Patent application title: FLUID TRANSFER DEVICE AND AN ACTIVE SUBSTANCE CARTRIDGE FOR THE FLUID TRANSFER DEVICE, AND A METHOD FOR CONTROLLING THE PRESSURE AT WHICH AN ACTIVE SUBSTANCE IS DELIVERED TO A SUBJECT FROM A FLUID TRANSFER DEVICE

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Abstract:

A micro-needle device comprising an active substance layer (3) having a
plurality of active substance chambers (4) formed therein, a drive
substance layer (9) having a plurality of drive substance chambers (10)
formed therein and a needle support layer (5) having a plurality of
micro-needles (6) extending therefrom. An activation layer (12)
comprising a plurality of heating elements (14) for heating an expandable
drive substance (11) located in the drive substance chambers (10) for in
turn urging the second membrane (16) into the active substance chamber
(4) for pressurising and urging an active substance (2) therefrom through
the corresponding micro-needle (6). A plurality of membrane accommodating
recesses (25) extend into the needle support layer (5) for accommodating
the first membrane (15) as the active substance in the corresponding
active substance chamber (10) is pressurised. A puncturing member (33)
with a piercing point (35) extends into each membrane accommodating
recess (25). A barrier grating (41) extends across each active substance
chamber (4) for preventing contact between the second membrane (16) and
the corresponding puncturing member (33).

Claims:

1-284. (canceled)

285. A fluid transfer device comprising a first layer having a first face
and a first chamber located in the first layer, a skin abutting layer
having a first face for abutting skin of a subject and a second face
located adjacent the first face of the first layer, a communicating means
in the skin abutting layer for accommodating a fluid between the first
chamber and the subject, a pressure altering means for altering the
pressure in the first chamber for urging the fluid between the first
chamber and the subject through the communicating means, a first membrane
located between the first face of the first layer and the second face of
the skin abutting layer for isolating the communicating means from the
first chamber, and a puncturing means located in one of the skin abutting
layer and the first layer to be engageable with the first membrane for
bursting thereof in response to the pressure altering means altering the
pressure in the first chamber.

286. A fluid transfer device as claimed in claim 285 in which the
puncturing means extends from one of the skin abutting layer and the
first layer and terminates in a piercing means for piercing the first
membrane, and preferably, the puncturing means terminates in the piercing
means at a location adjacent the first membrane, but slightly spaced
apart therefrom.

287. A fluid transfer device as claimed in claim 286 in which a membrane
accommodating recess extends into the skin abutting layer from the second
face thereof, and the puncturing means extends from the skin abutting
layer into the membrane accommodating recess towards the first membrane,
and preferably, the piercing means of the puncturing means is located
within the membrane accommodating recess adjacent a plane defined by the
second face of the skin abutting layer, and slightly spaced apart
therefrom, and advantageously, the piercing means is centrally located in
the membrane accommodating recess, and preferably, the communicating
means extends from the membrane accommodating recess, and preferably, the
membrane accommodating recess is communicable with the first chamber.

288. A fluid transfer device as claimed in claim 286 in which the spacing
between the piercing means and the first membrane is set to determine the
pressure in the first chamber at which the first membrane bursts, and
preferably, the puncturing means comprises an elongated puncturing member
terminating in the piercing means, and preferably, the piercing means is
defined by a piercing point, alternatively, the piercing means is defined
by a piercing edge, and preferably, the piercing means is defined by an
elongated piercing edge, and advantageously, the piercing edge defines a
sharp cutting edge, and preferably, the piercing edge defines a serrated
edge, and advantageously, the piercing edge is inclined relative to the
plane defined by the second face of the skin abutting layer for
progressively engaging the first membrane, and preferably, the piercing
edge is of partly annular shape, and advantageously, the piercing edge
extends around a substantial part of the membrane accommodating recess
adjacent the periphery thereof.

289. A fluid transfer device as claimed in claim 285 in which the first
membrane is moveable from a position spaced apart from the puncturing
means into engagement with the puncturing means in response to the
pressure altering means altering the pressure in the first chamber, and
preferably, the first membrane comprises a burstable material, and
preferably, the first membrane comprises a foil material, and
advantageously, the foil of the first membrane is a metal foil,
alternatively, the first membrane comprises a polymer film, and
preferably, an area of weakness is provided in the first membrane
co-operable with the puncturing means for bursting the first membrane,
and preferably, the first membrane is impermeable to the fluid to be
transferred between the first chamber and the subject, and
advantageously, the first membrane is secured to the first face of the
first layer for sealably closing the first chamber adjacent the first
face of the first layer, and preferably, the first membrane is secured to
the second face of the skin abutting layer for sealably closing the
membrane accommodating recess adjacent the second face of the skin
abutting layer, and preferably, a first alignment means is provided for
aligning the first chamber in the first layer with the communicating
means in the skin abutting layer, and advantageously, the first layer
comprises a polymer material, and preferably, the skin abutting layer
comprises a polymer material.

290. A fluid transfer device as claimed in claim 285 in which the first
layer defines a second face and the first chamber extends into the first
layer from the second face, a second membrane being located adjacent the
second face of the first layer for closing the first chamber adjacent the
second face of the first layer, the pressure altering means being
co-operable with the second membrane for urging the second membrane
relative to the first chamber for altering the pressure in the first
chamber, and preferably, the pressure altering means is co-operable with
the second membrane for one of increasing the pressure in the first
chamber and decreasing the pressure in the first chamber, and preferably,
the second membrane comprises a stretchable material, and advantageously,
the second membrane is impermeable to the fluid to be transferred between
the first chamber and the subject, and preferably, the second membrane is
secured to the second face of the first layer for sealably closing the
first chamber adjacent the second face of the first layer, and
advantageously, the first chamber extends through the first layer from
the first face to the second face.

291. A fluid transfer device as claimed in claim 290 in which a barrier
means is provided for preventing engagement of the second membrane with
the puncturing means, and preferably, the barrier means is permeable to
the fluid to be transferred between the first chamber and the subject,
and preferably, the barrier means is located in the first chamber, and
advantageously, the barrier means is located adjacent the first face of
the first chamber, and preferably, the barrier means extends across the
first chamber, and advantageously, the barrier means comprises a
perforated barrier panel, and preferably, the barrier panel defines a
plurality of openings extending therethrough, the openings being of size
to accommodate the fluid to be transferred between the first chamber and
the subject, but to prevent the second membrane passing therethrough, and
advantageously, the barrier means comprises a grating, and preferably,
the barrier means comprises a grill, and advantageously, the barrier
means defines a portion of the first face of the first layer, and
preferably, the first membrane is not secured to the barrier means to
facilitate movement of the first membrane relative to the barrier means.

292. A fluid transfer device as claimed in claim 290 in which a second
layer is provided having a first face and a second chamber extending into
the second layer from the first face thereof, the second layer being
located adjacent the first layer with the first face of the second layer
adjacent the second face of the first layer, and the second membrane
located between the first face of the second layer and the second face of
the first layer, and preferably, the second membrane is secured to the
first face of the second layer for sealably closing the second chamber
adjacent the first face of the second layer, and advantageously, a second
alignment means is provided for aligning the first chamber in the first
layer with the second chamber in the second layer, and preferably, the
second layer comprises a polymer material, and advantageously, the
pressure altering means is located in the second chamber of the second
layer, and preferably, the second chamber is aligned with the first
chamber, and advantageously, the pressure altering means comprises a
drive substance in the second chamber adapted to one of expand and
contract for urging the second membrane to one of increase the pressure
in the first chamber and to decrease the pressure in the first chamber,
and preferably, the second membrane is impermeable to the drive
substance, and advantageously, the drive substance comprises an
expandable material, and preferably, the drive substance is expandable in
response to heat, and advantageously, the drive substance comprises a
plurality of gas filled polymer micro-beads.

293. A fluid transfer device as claimed in claim 292 in which an
activating means is provided for activating the pressure altering means
to alter the pressure in the first chamber, and preferably, the second
layer defines a second face, and advantageously, an activation layer
defining a first face is located adjacent the second layer with the first
face of the activation layer adjacent the second face of the second
layer, and the activating means is located on the activation layer
adjacent the first face thereof for co-operating with the second chamber
for activating the pressure altering means therein for one of increasing
and decreasing the pressure in the first chamber of the first layer, and
preferably, the pressure altering means is responsive to heat for one of
increasing and decreasing the pressure in the first chamber, and the
activating means comprises a heating means, and advantageously, the
heating means comprises a heating element, and preferably, the heating
means comprises an electrically powered heating element, and
advantageously, the activating means is aligned with the second chamber.

294. A fluid transfer device as claimed in claim 293 in which the second
chamber extends through the second layer from the first face thereof to
the second face thereof, and preferably, a third membrane is located
between the second face of the second layer and the first face of the
activation layer for sealably closing the second chamber adjacent the
second face of the second layer, and advantageously, the third membrane
is of a heat insulating material, and a heat conducting means extends
through the third membrane for communicating heat from the heating means
to the second chamber, and preferably, the third membrane is impermeable
to the drive substance, and advantageously, the third membrane is secured
to the second face of the second layer for sealably closing the second
chamber adjacent the second face of the second layer, and preferably, a
third alignment means is provided for aligning the activating means in
the activation layer with the second chamber in the second layer.

295. A fluid transfer device as claimed in claim 285 in which a
penetrating means is provided on the first face of the skin abutting
layer for penetrating the skin of the subject, and preferably, the
penetrating means comprises a micro-needle extending from the first face
of the skin abutting layer, and preferably, the micro-needle terminates
in a distal skin penetrating tip, and preferably, the communicating means
extends through the micro-needle, and preferably, the communicating means
comprises a first communicating bore extending through the skin abutting
layer, and preferably, the communicating means comprises a second
communicating bore extending through the micro-needle communicating with
the first communicating bore, and advantageously, the micro-needle
defines a longitudinally extending central axis, and the second
communicating bore extends through the micro-needle offset from the
central axis, and preferably, the second communicating bore terminates in
an outer surface of the micro-needle spaced apart from the skin
penetrating tip, alternatively, the communicating means comprises a
communicating channel extending along an outer surface of the
micro-needle communicating with the first communicating bore extending
through the skin abutting layer, and preferably, the communicating
channel is recessed into the outer surface of the micro-needle, and
advantageously, the communicating channel terminates at a location spaced
apart from the distal skin penetrating tip, and preferably, the first
communicating bore extends from the membrane accommodating recess.

296. A fluid transfer device as claimed in claim 285 in which the device
is adapted for transferring a fluid from the first chamber to the
subject, and preferably, the fluid comprises a liquid active substance,
and advantageously, the liquid active substance comprises a liquid
medicament.

297. A fluid transfer device as claimed in claim 285 in which the first
layer comprises a plurality of first chambers, and one communicating
means extending through the skin abutting layer is provided corresponding
to each first chamber, each communicating means being communicable with
the corresponding first chamber, and preferably, a plurality of pressure
altering means are provided, and advantageously, one pressure altering
means is provided corresponding with each first chamber, and preferably,
one puncturing means is provided corresponding to each first chamber, and
advantageously, a plurality of second chambers are located in the second
layer, and preferably, one second chamber is provided corresponding to
each first chamber, the second chambers being aligned with the respective
first chambers, and advantageously, a plurality of micro-needles are
provided extending from the first surface of the skin abutting layer, and
preferably, one micro-needle is provided corresponding to each first
chamber, and advantageously, the first chambers are configured in the
first layer in a matrix.

298. A fluid transfer device as claimed in claim 285 in which a seal
effecting means is provided for effecting a seal between the first
membrane and the first layer adjacent the corresponding first chamber,
and preferably, each seal effecting means comprises an annular projecting
element extending from one of the first face of the first layer and the
second face of the skin abutting layer for engaging the first membrane to
effect the seal between the first membrane and the first layer, and
preferably, each annular projecting element terminates in a radiused
membrane abutting surface, and advantageously, each annular projecting
element extends from the first face of the first layer around the
corresponding first chamber, and preferably, each annular projecting
element extends from the second face of the skin abutting layer around
the corresponding communicating means, and advantageously, a gasket is
provided between the first membrane and one of the first layer and the
skin abutting layer, and preferably, a gasket accommodating recess
extends into the one of the first layer adjacent the first face of the
first layer and the skin abutting layer adjacent the second face thereof
for accommodating the gasket to co-operate with each annular projecting
element extending from the other one of the first layer and the skin
abutting layer for effecting the seal between the first membrane and the
first layer, and advantageously, the gasket is located in the gasket
accommodating recess for sealably engaging the first membrane between the
gasket and each annular projecting element, and preferably, the first
membrane is located between the gasket and the one or more annular
projecting elements, and advantageously, the gasket is of a deformable
material, and preferably, the gasket is of a resilient deformable
material, alternatively, a pair of annular projecting elements are
provided, one of said annular projecting elements extending from the
first face of the first layer and the other of the said pair of annular
projecting elements extending from the second face of the skin abutting
layer, the respective annular projecting elements co-operating with each
other to sealably engage the first membrane therebetween, alternatively,
the seal effecting means comprises a pair of interengageable
complementary formations, one of the interengageable complementary
formations being formed on the first face of the first layer, and the
other of the interengageable complementary formations being formed on the
second face of the skin abutting layer, the respective formations being
located adjacent and extending around the first chamber, and
advantageously, one of the interengageable complementary formations
comprises an annular projecting element, and the other of the
interengageable complementary formations comprises a recess, and
preferably, the annular recess extends into the one of the first face of
the first layer around and adjacent the first chamber and the second face
of the skin abutting layer around and adjacent the membrane accommodating
recess, and the annular projecting element extends from the other one of
the first face of the first layer around and adjacent the first chamber
and the second face of the skin abutting layer around and adjacent the
membrane accommodating recess, and advantageously, the annular recess
extends into the first face of the first layer, and preferably, a seal
effecting means is provided for effecting a seal between the second
membrane and the second face of the first layer adjacent the first
chamber, and advantageously, the seal effecting means comprises an
annular projecting element extending from one of the first face of the
second layer and the second surface of the first layer for engaging the
second membrane to effect the seal between the second membrane and the
first layer, and preferably, the annular projecting element terminates in
a radiused membrane abutting surface, and advantageously, each annular
projecting element extends from the first face of the second layer around
the corresponding second chamber, and preferably, each annular projecting
element extends from the second face of the first layer around the
corresponding first chamber, and preferably, a gasket is provided between
the second membrane and one of the first layer and the second layer, and
advantageously, a gasket accommodating recess extends into the one of the
first layer adjacent the second face of the first layer and the second
layer adjacent the first face thereof for accommodating the gasket to
co-operate with the corresponding annular projecting element extending
from the other one of the first layer and the second layer for effecting
the seal between the second membrane and the first layer, and preferably,
the gasket is located in the gasket accommodating recess for sealably
engaging the second membrane between the gasket and each annular
projecting element, and advantageously, the second membrane is located
between the gasket and the one or more annular projecting elements, and
preferably, the gasket is of a deformable material, and advantageously,
the gasket is of a resilient deformable material, alternatively, a pair
of annular projecting elements are provided, one of said annular elements
extending from the second face of the first layer and the other of the
said pair of annular projecting elements extending from the first face of
the second layer, the respective annular projecting elements co-operating
with each other to sealably engage the second membrane therebetween,
alternatively, the seal effecting means comprises a pair of
interengageable complementary formations, one of the interengageable
complementary formations being formed on the second face of the first
layer, and the other of the interengageable complementary formations
being formed on the first face of the second layer, the respective
formations being located adjacent and extending around the first chamber,
and preferably, one of the interengageable complementary formations
comprises an annular projecting ring, and the other of the
interengageable complementary formations comprises an annular recess, and
preferably, the annular recess extends into the one of the first face of
the second layer around and adjacent the second chamber and the second
face of the first layer around and adjacent the first chamber, and the
annular projecting element extends from the other one of the first face
of the second layer around and adjacent the second chamber, and the
second face of the first layer around and adjacent the first chamber, and
advantageously, the annular recess extends into the second face of the
second layer.

299. An active substance cartridge comprising a first layer having a
first face and a second face and at least one first chamber for an active
substance located in the first layer, a first membrane secured to the
first face for sealably closing the at least one first chamber adjacent
the first face of the first layer, a second membrane secured to the
second face of the first layer for sealably closing the at least one
first chamber adjacent the second face of the first layer, and a barrier
means located in the at least one first chamber for preventing passage of
the second membrane across the barrier means, the barrier means being
permeable to the active substance.

300. An active substance cartridge as claimed in claim 299 in which each
barrier means extends across the corresponding first chamber, and
preferably, each barrier means is located adjacent the first face of the
first layer, and advantageously, each barrier means defines a portion of
the first face of the first layer, and preferably, the portion of the
first face of the first layer defined by each barrier means and the first
face of the first layer are coplanar, and preferably, the first membrane
is not secured to the barrier means so that a portion of the first
membrane adjacent each barrier means is moveable relative to the barrier
means, and advantageously, each barrier means comprises a perforated
barrier panel, and preferably, the barrier panel of each barrier means
defines a plurality of openings extending therethrough, the openings
being of size to accommodate the active substance therethrough, but to
prevent the second membrane passing therethrough, and advantageously,
each barrier means comprises a grating, and preferably, each barrier
means comprises a grill.

301. An active substance cartridge as claimed in claim 299 in which a
plurality of first chambers are provided in the first layer, and
preferably, the first chambers are configured in a matrix, and
preferably, each first chamber comprises an active substance.

303. An active substance cartridge as claimed in claim 299 in which the
active substance cartridge is adapted for use in the fluid transfer
device as claimed in claim 285 in place of the first layer and the first
membrane thereof.

304. A micro-needle device comprising a first layer having a first face
and a first chamber located in the first layer, a needle support layer
having a first face and a second face for locating adjacent the first
face of the first layer, a micro-needle extending from the needle support
layer adjacent the first face thereof, a communicating means in the
needle support layer and the micro-needle for accommodating a fluid
between the first chamber and the subject, a pressure altering means for
altering the pressure in the first chamber for urging the fluid between
the first chamber and the subject through the communicating means, a
first membrane located between the first face of the first layer and the
second face of the needle support layer for isolating the communicating
means from the first chamber, and a puncturing means located in one of
the needle support layer and the first layer to be engageable with the
first membrane for bursting thereof in response to the pressure altering
means altering the pressure in the first chamber.

305. A method for controlling the pressure at which an active substance
is delivered from a fluid transfer device, the fluid transfer device
comprising a first layer having a first face and a first chamber for the
active substance located in the first layer, a skin abutting layer having
a first face for abutting the skin of the subject and a second face
located adjacent the first face of the first layer, skin penetrating
means extending from the first face of the skin abutting layer, a
communicating means in the skin abutting layer for accommodating the
active substance from the first chamber to the subject, a pressure
altering means for increasing the pressure in the first chamber for
urging the active substance from the first chamber to the subject through
the communicating means, a first membrane located between the first face
of the first layer and the second face of the skin abutting layer for
isolating the communicating means from the first chamber, and a
puncturing means located in the skin abutting layer engageable with the
first membrane for bursting thereof on movement of the first membrane in
response to the pressure altering means increasing the pressure in the
first chamber, the method comprising setting the puncturing means
relative to the first membrane so that the first membrane engages the
puncturing means for bursting thereof when the pressure in the first
chamber has increased to a pressure approximately equal to the pressure
at which the active substance is to be delivered from the fluid transfer
device, in order to set the velocity at which the active substance is
delivered to the subject.

Description:

[0001] The present invention relates to a fluid transfer device for
transferring a fluid between the device and a subject, and in particular
the invention relates to a transfer device for delivering an active
substance from the device to a subject intradermally, transdermally,
subcutaneously or intramuscularly. The invention also relates to a
transfer device for drawing a fluid from a subject. Such devices may be
micro-needle devices or otherwise. The invention also relates to an
active substance cartridge containing an active substance for use in such
a fluid transfer or micro-needle device, and the invention also relates
to a method for controlling the pressure at which an active substance is
delivered to a subject from a fluid transfer device, such as a
micro-needle device.

[0002] Micro-needle devices are commonly used for delivering a medicament
in fluid form, typically, in liquid form, intradermally, transdermally,
subcutaneously and intramuscularly to a subject. Such micro-needle
devices, in general, comprise an active substance layer, which typically
is of a polymer material defining a first major surface and a second
major surface. A plurality of bores, in general, cylindrical bores extend
through the active substance layer from the first major surface to the
second major surface to form respective active substance chambers for
holding similar or different active substances to be delivered to a
subject. The bores which form the active substance chambers, in general,
are arranged in the form of a matrix.

[0003] A needle support layer comprising a plurality of micro-needles
extending from a first major surface of the support layer are arranged in
a matrix similar to the matrix of the active substance chambers and are
aligned with the active substance chambers for accommodating the active
substance from corresponding ones of the active substance chambers to the
subject. A second major surface of the needle support layer is located
adjacent the first major surface of the active substance layer, and a
first membrane of a burstable material is located between the second
major surface of the needle support layer, and the first major surface of
the active substance layer and is sealably secured thereto for sealably
closing the active substance chambers adjacent the first major surface of
the active substance layer. A plurality of communicating bores extending
through the needle support layer extend through corresponding ones of the
micro-needles for communicating the active substance chambers with the
subject when the first membrane has been burst.

[0004] A drive substance layer which defines first and second opposite
major surfaces is provided with a plurality of drive substance chambers
which are arranged in a matrix similar to the matrix of the active
substance chambers, and are aligned with corresponding ones of the active
substance chambers. A second membrane of a stretchable material is
located between and sealably secured to the second major surface of the
active substance layer and the first major surface of the drive substance
layer for sealably closing the active substance chambers adjacent the
second major surface of the active substance layer and for sealably
closing the drive substance chambers adjacent the first major surface of
the drive substance layer.

[0005] A drive substance, typically, an expandable material which expands
under heat is located in the drive substance chambers for urging the
stretchable second membrane into the corresponding active substance
chambers for pressurising the active substance in the active substance
chambers to firstly burst the first membrane adjacent the active
substance chambers to communicate the active substance chambers with the
corresponding micro-needles for delivering the active substance from the
active substance chambers. An activation layer which comprises a
plurality of heating elements arranged in a matrix similar to the matrix
of the drive substance chambers and aligned with the drive substance
chambers is located adjacent the drive substance layer for heating the
drive substance contained in the drive substance chambers. A third
membrane located between the second major surface of the drive substance
layer and a first major surface of the activation layer sealably closes
the drive substance chambers.

[0006] Such micro-needle devices will be known to those skilled in the
art.

[0007] However, such micro-needle devices suffer from two relatively
serious disadvantages. Firstly, the first membrane of the burstable
material which is located between the active substance layer and the
needle support layer must be burst adjacent the active substance chamber
from which the active substance is to be delivered to the subject in
order that the active substance chamber can communicate with the
communicating bore of the corresponding micro-needle. The bursting of the
first membrane is achieved by pressurising the active substance so that
when the pressure of the active substance acting on the first membrane
reaches a sufficient bursting pressure, the first membrane adjacent the
relevant active substance chamber bursts. However, firstly, there is no
guarantee that the pressure of the active substance will be sufficient to
burst the first membrane, and secondly, the pressure at which the first
membrane is burst may vary relatively dramatically from active substance
chamber to active substance chamber depending on the quality and
consistency of the first membrane.

[0008] A second disadvantage of known micro-needle devices is that it is
virtually impossible to control the pressure at which the active
substance is delivered to the subject, and thus, it is impossible to
control the depth beneath the skin of the subject to which the active
substance is delivered to the subject.

[0009] These disadvantages are undesirable, and there is therefore a need
for a micro-needle device which addresses at least one of the
disadvantages of known micro-needle devices.

[0010] The present invention is directed towards providing a micro-needle
device which addresses at least one of the disadvantages of known
micro-needle devices. The invention is also directed towards providing a
fluid transfer device for transferring a substance between the device and
a subject, and the invention is also directed towards providing an active
substance cartridge for use in a micro-needle device or a fluid transfer
device. The invention is also directed towards providing a method for
controlling the pressure at which an active substance is delivered from a
fluid transfer device to a subject.

[0011] According to the invention there is provided a fluid transfer
device comprising a first layer having a first face and a first chamber
located in the first layer, a skin abutting layer having a first face for
abutting skin of a subject and a second face located adjacent the first
face of the first layer, a communicating means in the skin abutting layer
for accommodating a fluid between the first chamber and the subject, a
pressure altering means for altering the pressure in the first chamber
for urging the fluid between the first chamber and the subject through
the communicating means, a first membrane located between the first face
of the first layer and the second face of the skin abutting layer for
isolating the communicating means from the first chamber, and a
puncturing means located in one of the skin abutting layer and the first
layer to to be engageable with the first membrane for bursting thereof in
response to the pressure altering means altering the pressure in the
first chamber.

[0012] In one embodiment of the invention the puncturing means extends
from one of the skin abutting layer and the first layer and terminates in
a piercing means for piercing the first membrane. Preferably, the
puncturing means terminates in the piercing means at a location adjacent
the first membrane, but slightly spaced apart therefrom.

[0013] Advantageously, a membrane accommodating recess extends into the
skin abutting layer from the second face thereof, and the puncturing
means extends from the skin abutting layer into the membrane
accommodating recess towards the first membrane. Preferably, the piercing
means of the puncturing means is located within the membrane
accommodating recess adjacent a plane defined by the second face of the
skin abutting layer, and slightly spaced apart therefrom. Ideally, the
piercing means is centrally located in the membrane accommodating recess.

[0014] Preferably, the communicating means extends from the membrane
accommodating recess. Advantageously, the membrane accommodating recess
is communicable with the first chamber.

[0015] In one embodiment of the invention the spacing between the piercing
means and the first membrane is set to determine the pressure in the
first chamber at which the first membrane bursts.

[0016] Preferably, the puncturing means comprises an elongated puncturing
member terminating in the piercing means.

[0017] In one embodiment of the invention the piercing means is defined by
a piercing point. Alternatively, the piercing means is defined by a
piercing edge.

[0018] In another embodiment of the invention the piercing means is
defined by an elongated piercing edge. Preferably, the piercing edge
defines a sharp cutting edge. Alternatively, the piercing edge defines a
serrated edge.

[0019] In another embodiment of the invention the piercing edge is
inclined relative to the plane defined by the second face of the skin
abutting layer for progressively engaging the first membrane.
Advantageously, the piercing edge is of partly annular shape. Preferably,
the piercing edge extends around a substantial part of the membrane
accommodating recess adjacent the periphery thereof.

[0020] In one embodiment of the invention the first membrane is moveable
from a position spaced apart from the puncturing means into engagement
with the puncturing means in response to the pressure altering means
altering the pressure in the first chamber. Preferably, the first
membrane comprises a burstable material.

[0021] In one embodiment of the invention the first membrane comprises a
foil material.

[0022] In another embodiment of the invention the foil of the first
membrane is a metal foil.

[0023] Alternatively, the first membrane comprises a polymer film.

[0024] In another embodiment of the invention an area of weakness is
provided in the first membrane co-operable with the puncturing means for
bursting the first membrane.

[0025] Preferably, the first membrane is impermeable to the fluid to be
transferred between the first chamber and the subject. Advantageously,
the first membrane is secured to the first face of the first layer for
sealably closing the first chamber adjacent the first face of the first
layer.

[0026] Preferably, the first membrane is secured to the second face of the
skin abutting layer for sealably closing the membrane accommodating
recess adjacent the second face of the skin abutting layer.

[0027] In one embodiment of the invention a first alignment means is
provided for aligning the first chamber in the first layer with the
communicating means in the skin abutting layer.

[0028] In one embodiment of the invention the first layer comprises a
polymer material.

[0029] In another embodiment of the invention the skin abutting layer
comprises a polymer material.

[0030] In a further embodiment of the invention the first layer defines a
second face and the first chamber extends into the first layer from the
second face, a second membrane being located adjacent the second face of
the first layer for closing the first chamber adjacent the second face of
the first layer, the pressure altering means being co-operable with the
second membrane for urging the second membrane relative to the first
chamber for altering the pressure in the first chamber. Preferably, the
pressure altering means is co-operable with the second membrane for one
of increasing the pressure in the first chamber and decreasing the
pressure in the first chamber. Advantageously, the second membrane
comprises a stretchable material. Preferably, the second membrane is
impermeable to the fluid to be transferred between the first chamber and
the subject.

[0031] In one embodiment of the invention the second membrane is secured
to the second face of the first layer for sealably closing the first
chamber adjacent the second face of the first layer.

[0032] In another embodiment of the invention the first chamber extends
through the first layer from the first face to the second face.

[0033] In a further embodiment of the invention a barrier means is
provided for preventing engagement of the second membrane with the
puncturing means. Preferably, the barrier means is permeable to the fluid
to be transferred between the first chamber and the subject.
Advantageously, the barrier means is located in the first chamber.

[0034] Ideally, the barrier means is located adjacent the first face of
the first chamber, and advantageously, the barrier means extends across
the first chamber.

[0035] In one embodiment of the invention the barrier means comprises a
perforated barrier panel. Preferably, the barrier panel defines a
plurality of openings extending therethrough, the openings being of size
to accommodate the fluid to be transferred between the first chamber and
the subject, but to prevent the second membrane passing therethrough.
Preferably, the barrier means comprises a grating. Advantageously, the
barrier means comprises a grill.

[0036] In one embodiment of the invention the barrier means defines a
portion of the first face of the first layer, and preferably, the first
membrane is not secured to the barrier means to facilitate movement of
the first membrane relative to the barrier means.

[0037] In another embodiment of the invention a second layer is provided
having a first face and a second chamber extending into the second layer
from the first face thereof, the second layer being located adjacent the
first layer with the first face of the second layer adjacent the second
face of the first layer, and the second membrane located between the
first face of the second layer and the second face of the first layer.

[0038] Preferably, the second membrane is secured to the first face of the
second layer for sealably closing the second chamber adjacent the first
face of the second layer.

[0039] In one embodiment of the invention a second alignment means is
provided for aligning the first chamber in the first layer with the
second chamber in the second layer.

[0040] In a further embodiment of the invention the second layer comprises
a polymer material.

[0041] Preferably, the pressure altering means is located in the second
chamber of the second layer.

[0042] Advantageously, the second chamber is aligned with the first
chamber.

[0043] In one embodiment of the invention the pressure altering means
comprises a drive substance in the second chamber adapted to one of
expand and contract for urging the second membrane to one of increase the
pressure in the first chamber and to decrease the pressure in the first
chamber.

[0044] Preferably, the second membrane is impermeable to the drive
substance.

[0045] Advantageously, the drive substance comprises an expandable
material, and preferably, the drive substance is expandable in response
to heat.

[0046] In one embodiment of the invention the drive substance comprises a
plurality of gas filled polymer micro-beads.

[0047] In another embodiment of the invention an activating means is
provided for activating the pressure altering means to alter the pressure
in the first chamber.

[0048] In another embodiment of the invention the second layer defines a
second face.

[0049] In a further embodiment of the invention an activation layer
defining a first face is located adjacent the second layer with the first
face of the activation layer adjacent the second face of the second
layer, and the activating means is located on the activation layer
adjacent the first face thereof for co-operating with the second chamber
for activating the pressure altering means therein for one of increasing
and decreasing the pressure in the first chamber of the first layer.

[0050] Preferably, the pressure altering means is responsive to heat for
one of increasing and decreasing the pressure in the first chamber, and
the activating means comprises a heating means. Advantageously, the
heating means comprises a heating element.

[0051] In one embodiment of the invention the heating means comprises an
electrically powered heating element.

[0052] Preferably, the activating means is aligned with the second
chamber.

[0053] In one embodiment of the invention the second chamber extends
through the second layer from the first face thereof to the second face
thereof.

[0054] In another embodiment of the invention a third membrane is located
between the second face of the second layer and the first face of the
activation layer for sealably closing the second chamber adjacent the
second face of the second layer. Preferably, the third membrane is of a
heat insulating material, and a heat conducting means extends through the
third membrane for communicating heat from the heating means to the
second chamber. Advantageously, the third membrane is impermeable to the
drive substance.

[0055] In one embodiment of the invention the third membrane is secured to
the second face of the second layer for sealably closing the second
chamber adjacent the second face of the second layer.

[0056] In another embodiment of the invention a third alignment means is
provided for aligning the activating means in the activation layer with
the second chamber in the second layer.

[0057] Preferably, a penetrating means is provided on the first face of
the skin abutting layer for penetrating the skin of the subject.
Advantageously, the penetrating means comprises a micro-needle extending
from the first face of the skin abutting layer. Ideally, the micro-needle
terminates in a distal skin penetrating tip.

[0058] In one embodiment of the invention the communicating means extends
through the micro-needle.

[0059] In another embodiment of the invention the communicating means
comprises a first communicating bore extending through the skin abutting
layer.

[0060] In another embodiment of the invention the communicating means
comprises a second communicating bore extending through the micro-needle
communicating with the first communicating bore.

[0061] In a further embodiment of the invention the micro-needle defines a
longitudinally extending central axis, and the second communicating bore
extends through the micro-needle offset from the central axis.
Preferably, the second communicating bore terminates in an outer surface
of the micro-needle spaced apart from the skin penetrating tip.

[0062] Alternatively, the communicating means comprises a communicating
channel extending along an outer surface of the micro-needle
communicating with the first communicating bore extending through the
skin abutting layer. Preferably, the communicating channel is recessed
into the outer surface of the micro-needle. Advantageously, the
communicating channel terminates at a location spaced apart from the
distal skin penetrating tip. Preferably, the first communicating bore
extends from the membrane accommodating recess.

[0063] In one embodiment of the invention the device is adapted for
transferring a fluid from the first chamber to the subject, and
preferably, the fluid comprises a liquid active substance, and
advantageously, the liquid active substance comprises a liquid
medicament.

[0064] In one embodiment of the invention the first layer comprises a
plurality of first chambers, and one communicating means extending
through the skin abutting layer is provided corresponding to each first
chamber, each communicating means being communicable with the
corresponding first chamber.

[0065] In another embodiment of the invention a plurality of pressure
altering means are provided. Preferably, one pressure altering means is
provided corresponding with each first chamber.

[0066] Preferably, one puncturing means is provided corresponding to each
first chamber.

[0067] In another embodiment of the invention a plurality of second
chambers are located in the second layer. Preferably, one second chamber
is provided corresponding to each first chamber, the second chambers
being aligned with the respective first chambers.

[0068] In another embodiment of the invention a plurality of micro-needles
are provided extending from the first surface of the skin abutting layer.
Preferably, one micro-needle is provided corresponding to each first
chamber.

[0069] In one embodiment of the invention the first chambers are
configured in the first layer in a matrix.

[0070] In another embodiment of the invention a seal effecting means is
provided for effecting a seal between the first membrane and the first
layer adjacent the corresponding first chamber.

[0071] In one embodiment of the invention each seal effecting means
comprises an annular projecting element extending from one of the first
face of the first layer and the second face of the skin abutting layer
for engaging the first membrane to effect the seal between the first
membrane and the first layer. Preferably, each annular projecting element
terminates in a radiused membrane abutting surface.

[0072] In one embodiment of the invention each annular projecting element
extends from the first face of the first layer around the corresponding
first chamber. Alternatively, each annular projecting element extends
from the second face of the skin abutting layer around the corresponding
communicating means.

[0073] In another embodiment of the invention a gasket is provided between
the first membrane and one of the first layer and the skin abutting
layer.

[0074] In another embodiment of the invention a gasket accommodating
recess extends into the one of the first layer adjacent the first face of
the first layer and the skin abutting layer adjacent the second face
thereof for accommodating the gasket to co-operate with each annular
projecting element extending from the other one of the first layer and
the skin abutting layer for effecting the seal between the first membrane
and the first layer. Preferably, the gasket is located in the gasket
accommodating recess for sealably engaging the first membrane between the
gasket and each annular projecting element. Advantageously, the first
membrane is located between the gasket and the one or more annular
projecting elements. Preferably, the gasket is of a deformable material.
Ideally, the gasket is of a resilient deformable material.

[0075] Alternatively, a pair of annular projecting elements are provided,
one of said annular projecting elements extending from the first face of
the first layer and the other of the said pair of annular projecting
elements extending from the second face of the skin abutting layer, the
respective annular projecting elements co-operating with each other to
sealably engage the first membrane therebetween.

[0076] In an alternative embodiment of the invention the seal effecting
means comprises a pair of interengageable complementary formations, one
of the interengageable complementary formations being formed on the first
face of the first layer, and the other of the interengageable
complementary formations being formed on the second face of the skin
abutting layer, the respective formations being located adjacent and
extending around the first chamber.

[0077] Preferably, one of the interengageable complementary formations
comprises an annular projecting element, and the other of the
interengageable complementary formations comprises a recess.
Advantageously, the annular recess extends into the one of the first face
of the first layer around and adjacent the first chamber and the second
face of the skin abutting layer around and adjacent the membrane
accommodating recess, and the annular projecting element extends from the
other one of the first face of the first layer around and adjacent the
first chamber and the second face of the skin abutting layer around and
adjacent the membrane accommodating recess. Preferably, the annular
recess extends into the first face of the first layer.

[0078] In another embodiment of the invention a seal effecting means is
provided for effecting a seal between the second membrane and the second
face of the first layer adjacent the first chamber.

[0079] In another embodiment of the invention the seal effecting means
comprises an annular projecting element extending from one of the first
face of the second layer and the second surface of the first layer for
engaging the second membrane to effect the seal between the second
membrane and the first layer. Preferably, the annular projecting element
terminates in a radiused membrane abutting surface.

[0080] In one embodiment of the invention each annular projecting element
extends from the first face of the second layer around the corresponding
second chamber. Alternatively, each annular projecting element extends
from the second face of the first layer around the corresponding first
chamber.

[0081] In one embodiment of the invention a gasket is provided between the
second membrane and one of the first layer and the second layer.

[0082] In another embodiment of the invention a gasket accommodating
recess extends into the one of the first layer adjacent the second face
of the first layer and the second layer adjacent the first face thereof
for accommodating the gasket to co-operate with the corresponding annular
projecting element extending from the other one of the first layer and
the second layer for effecting the seal between the second membrane and
the first layer. Preferably, the gasket is located in the gasket
accommodating recess for sealably engaging the second membrane between
the gasket and each annular projecting element. Advantageously, the
second membrane is located between the gasket and the one or more annular
projecting elements. Preferably, the gasket is of a deformable material.
Advantageously, the gasket is of a resilient deformable material.

[0083] In another embodiment of the invention a pair of annular projecting
elements are provided, one of said annular elements extending from the
second face of the first layer and the other of the said pair of annular
projecting elements extending from the first face of the second layer,
the respective annular projecting elements co-operating with each other
to sealably engage the second membrane therebetween.

[0084] In a further embodiment of the invention the seal effecting means
comprises a pair of interengageable complementary formations, one of the
interengageable complementary formations being formed on the second face
of the first layer, and the other of the interengageable complementary
formations being formed on the first face of the second layer, the
respective formations being located adjacent and extending around the
first chamber.

[0085] Preferably, one of the interengageable complementary formations
comprises an annular projecting ring, and the other of the
interengageable complementary formations comprises an annular recess.
Advantageously, the annular recess extends into the one of the first face
of the second layer around and adjacent the second chamber and the second
face of the first layer around and adjacent the first chamber, and the
annular projecting element extends from the other one of the first face
of the second layer around and adjacent the second chamber, and the
second face of the first layer around and adjacent the first chamber.

[0086] Preferably, the annular recess extends into the second face of the
second layer.

[0087] The invention also provides an active substance cartridge
comprising a first layer having a first face and a second face and at
least one first chamber for an active substance located in the first
layer, a first membrane secured to the first face for sealably closing
the at least one first chamber adjacent the first face of the first
layer, a second membrane secured to the second face of the first layer
for sealably closing the at least one first chamber adjacent the second
face of the first layer, and a barrier means located in the at least one
first chamber for preventing passage of the second membrane across the
barrier means, the barrier means being permeable to the active substance.

[0088] Preferably, each barrier means extends across the corresponding
first chamber. Advantageously, each barrier means is located adjacent the
first face of the first layer. Preferably, each barrier means defines a
portion of the first face of the first layer.

[0089] In one embodiment of the invention the portion of the first face of
the first layer defined by each barrier means and the first face of the
first layer are coplanar.

[0090] Advantageously, the first membrane is not secured to the barrier
means so that a portion of the first membrane adjacent each barrier means
is moveable relative to the barrier means. Preferably, each barrier means
comprises a perforated barrier panel.

[0091] In one embodiment of the invention the barrier panel of each
barrier means defines a plurality of openings extending therethrough, the
openings being of size to accommodate the active substance therethrough,
but to prevent the second membrane passing therethrough.

[0092] In one embodiment of the invention each barrier means comprises a
grating.

[0093] In another embodiment of the invention each barrier means comprises
a grill.

[0094] Preferably, each barrier means is of a polymer material.
Advantageously, each barrier means is integrally formed with the first
layer.

[0095] Preferably, the first layer is of a polymer material.

[0096] In another embodiment of the invention the second membrane
comprises a foil material.

[0097] In another embodiment of the invention the second membrane
comprises a metal foil material.

[0098] In another embodiment of the invention the second membrane
comprises a polymer film.

[0099] Alternatively, the second membrane comprises a stretchable
material.

[0100] Preferably, a plurality of first chambers are provided in the first
layer.

[0101] In another embodiment of the invention each first chamber comprises
an active substance. Preferably, the active substance is a medicament.

[0102] In another embodiment of the invention the active substances in the
respective first chambers are the same or different.

[0103] The invention also provides a fluid transfer device comprising the
active substance cartridge according to the invention.

[0104] The invention also provides a micro-needle device comprising the
active substance cartridge according to the invention.

[0105] Further the invention provides the active substance cartridge
adapted for use in the fluid transfer device according to the invention
with the active substance cartridge according to the invention in place
of the first layer and the first membrane of the fluid transfer device.

[0106] The invention also provides a micro-needle device comprising a
first layer having a first face and a first chamber located in the first
layer, a needle support layer having a first face and a second face for
locating adjacent the first face of the first layer, a micro-needle
extending from the needle support layer adjacent the first face thereof,
a communicating means in the needle support layer and the micro-needle
for accommodating a fluid between the first chamber and the subject, a
pressure altering means for altering the pressure in the first chamber
for urging the fluid between the first chamber and the subject through
the communicating means, a first membrane located between the first face
of the first layer and the second face of the needle support layer for
isolating the communicating means from the first chamber, and a
puncturing means located in one of the needle support layer and the first
layer to be engageable with the first membrane for bursting thereof in
response to the pressure altering means altering the pressure in the
first chamber.

[0107] Further the invention provides a method for controlling the
pressure at which an active substance is delivered from a fluid transfer
device, the fluid transfer device comprising a first layer having a first
face and a first chamber for the active substance located in the first
layer, a skin abutting layer having a first face for abutting the skin of
the subject and a second face located adjacent the first face of the
first layer, skin penetrating means extending from the first face of the
skin abutting layer, a communicating means in the skin abutting layer for
accommodating the active substance from the first chamber to the subject,
a pressure altering means for increasing the pressure in the first
chamber for urging the active substance from the first chamber to the
subject through the communicating means, a first membrane located between
the first face of the first layer and the second face of the skin
abutting layer for isolating the communicating means from the first
chamber, and a puncturing means located in the skin abutting layer
engageable with the first membrane for bursting thereof on movement of
the first membrane in response to the pressure altering means increasing
the pressure in the first chamber, the method comprising setting the
puncturing means relative to the first membrane so that the first
membrane engages the puncturing means for bursting thereof when the
pressure in the first chamber has increased to a pressure approximately
equal to the pressure at which the active substance is to be delivered
from the fluid transfer device.

[0108] Preferably, the puncturing means is spaced apart from the first
membrane, and the spacing between the puncturing means and the first
membrane is set.

[0109] Advantageously, the puncturing means terminates in a piercing means
and the spacing between the piercing means and the first membrane is set.

[0110] The advantages of the invention are many. The provision of the
puncturing means for puncturing the first membrane ensures that the first
membrane is punctured on the active substance being pressurised in the
corresponding first chamber. Additionally, by locating the puncturing
means in a membrane accommodating recess of the skin abutting layer and
by providing the puncturing means with a piercing means which is located
within the membrane accommodating recess and by setting the distance
between the piercing means and the first membrane at an appropriate
distance, the pressure of the active substance in the corresponding first
chamber at which the first membrane bursts can be set, and in turn, the
pressure at which the active substance is delivered from the first
chamber to the subject can likewise be set. This thus permits the
injection velocity at which the active substance is delivered to the
subject to be set at a desired target injection velocity, so that the
depth beneath the skin of the subject to which the active substance is
delivered can be set.

[0111] By providing the barrier means in the first chamber of the first
layer, the second stretchable membrane is separated from the puncturing
means, and thus, there is no danger of the second membrane being
punctured, and in turn there is no danger of contamination of the active
substance with the drive substance.

[0112] The provision of the seal effecting means for effecting a seal
between the first and second membranes and the corresponding skin
abutting layer, first layer and second layer ensures that a good seal is
achieved between the respective membranes and the skin abutting layer and
the first and second layers, thereby avoiding any danger of leakage of an
active substance from one first chamber to an adjacent first chamber and
similarly, avoiding any danger of leakage of a drive substance from one
second chamber to an adjacent second chamber.

[0113] Another advantage of the invention is achieved when the first
membrane is stretched taut across the one or more membrane accommodating
recesses, in that by stretching the first membrane across the one or more
membrane accommodating recesses, the reliability and accuracy with which
the pressure of the active substance at which the first membrane engages
the piercing means of the puncturing means, and in turn bursts can be
set.

[0114] The invention will be more clearly understood from the following
description of some preferred embodiments thereof, which are given by way
of example only, with reference to the accompanying drawings, in which:

[0115]FIG. 1 is a side elevational view not to scale of a micro-needle
device according to the invention,

[0116]FIG. 2 is a transverse cross-sectional end elevational view, also
not to scale, of a portion of the micro-needle device of FIG. 1,

[0117] FIG. 3 is an enlarged transverse cross-sectional end elevational
view, also not to scale, of a detail of the micro-needle device of FIG.
1,

[0118] FIG. 4 is an enlarged transverse cross-sectional end elevational
view, also not to scale, of the portion of FIG. 2 of the micro-needle
device of FIG. 1 in a different state,

[0119]FIG. 5 is a top plan view not to scale of another detail of the
micro-needle device of FIG. 1,

[0120] FIG. 6 is a perspective view not to scale of an active substance
cartridge also according to the invention for a micro-needle device,

[0121]FIG. 7 is a view similar to FIG. 2, and also not to scale, of a
portion of a micro-needle device according to another embodiment of the
invention,

[0122]FIG. 8 is a view similar to FIG. 4, and also not to scale, of the
micro-needle device of FIG. 7,

[0123] FIG. 9 is a top perspective view not to scale of a portion of a
micro-needle device according to another embodiment of the invention,

[0124] FIG. 10 is an underneath perspective view not to scale of the
portion of FIG. 9 of the micro-needle device according to the embodiment
of the invention of FIG. 9,

[0125] FIG. 11 is a view similar to FIG. 4 and also not to scale of a
micro-needle device according to another embodiment of the invention,

[0126]FIG. 12 is a view similar to FIG. 3 and also not to scale of a
detail of the micro-needle device of FIG. 11,

[0127] FIG. 13 is view similar to FIG. 5 and also not to scale of the
micro-needle device of FIG. 11,

[0128]FIG. 14 is a view similar to FIG. 2, and also not to scale, of a
portion of a micro-needle device according to a further embodiment of the
invention,

[0129]FIG. 15 is a side elevational view, not to scale, of a micro-needle
device according to a still further embodiment of the invention,

[0130] FIG. 16 is a view similar to FIG. 2, and also not to scale of a
portion of the micro-needle device of FIG. 15,

[0131]FIG. 17 is a cross-sectional side elevational view, also not to
scale, of a portion of a micro-needle device according to another
embodiment of the invention,

[0132]FIG. 18 is a top plan view of a detail of the micro-needle device
of FIG. 17,

[0133]FIG. 19 is a top plan view of the detail of FIG. 18 of the
micro-needle device of FIG. 17 with a portion of the detail removed, and

[0134]FIG. 20 is an underneath perspective view of another detail of the
micro-needle device of FIG. 17.

[0135] Referring to the drawings and initially to FIGS. 1 to 5 thereof,
there is illustrated a fluid transfer device according to the invention
for transferring a fluid between the device and the subject, which in
this case comprises a micro-needle device, indicated generally by the
reference numeral 1. The micro-needle device 1 is particularly suitable
for delivering an active substance in liquid form, for example, a liquid
medicament, intradermally, transdermally, subcutaneously as well as
intramuscularly to a subject at a preset pressure, so that the active
substance 2 is delivered at a target injection velocity to a
predetermined depth beneath the skin of the subject.

[0136] The micro-needle device 1 comprises a first layer, namely, an
active substance layer 3 having a plurality of first chambers, namely,
active substance chambers 4 for the active substance 2. For convenience
in FIGS. 2 and 4 only one active substance chamber 4 is illustrated. A
skin abutting layer, namely, a needle support layer 5, is secured to the
active substance layer 3 and comprises a plurality of penetrating means
for penetrating the skin of a subject, which in this embodiment of the
invention are provided by a plurality of micro-needles 6 extending from
the needle support layer 5. The micro-needles 6 correspond with and are
aligned with the active substance chambers 4 for accommodating the active
substance from the corresponding active substance chambers 4
intradermally, transdermally, subcutaneously and/or intramuscularly to
the subject.

[0137] A second layer, namely, a drive substance layer 9, is secured to
the active substance layer 3. The drive substance layer 9 comprises a
plurality of second chambers, namely, drive substance chambers 10, in
which are located a means for altering the pressure in the active
substance chambers 4, which in this embodiment of the invention comprises
a drive substance 11. In this case the drive substance 11 increases the
pressure in the active substance chambers 4 for urging the active
substance 2 therefrom through the micro-needles 6. The drive substance is
described in detail below.

[0138] An activation layer 12 comprising a plurality of activating means,
which in this embodiment of the invention are provided by heating means,
namely, electrically powered heating elements 14, is secured to the drive
substance layer 9 for activating the drive substance 11 in the drive
substance chambers 10 for increasing the pressure in the active substance
chambers 4 as will be described in detail below.

[0139] A first membrane 15 is located between the active substance layer 3
and the needle support layer 5, a second membrane 16 is located between
the active substance layer 3 and the drive substance layer 9, and a third
membrane 17 is located between the drive substance layer 9 and the
activation layer 12. The first, second and third membranes 15, 16 and 17
are described in detail below.

[0140] The active substance layer 3 is of a polymer material and defines a
first face, namely, a first major surface 20 and a second face, namely,
an opposite second major surface 21. The active substance chambers 4 are
formed in the active substance layer 3 by respective cylindrical bores
which extend in this case from the second major surface 21 into the
active substance layer 3. The active substance chambers 4 are arranged in
a matrix in the active substance layer 3, and are adapted for
accommodating the active substance 2. It is envisaged that different ones
of the active substance chambers 4 may be charged with respective
different active substances, depending on a treatment regime under which
the subject is to be treated.

[0141] The needle support layer 5 defines a first face, namely, a first
major surface 23 for abutting the skin of the subject, and from which the
micro-needles 6 extend, and a second face, namely, an opposite second
major surface 24 which is located adjacent the active substance layer 3.
The micro-needles 6 are disposed in a matrix which is similar to the
matrix in which the active substance chambers 4 are disposed in the
active substance layer 3, and are substantially aligned with the active
substance chambers 4, so that one micro-needle 6 is provided
corresponding to each active substance chamber 4. A plurality of
substantially dome shaped membrane accommodating recesses 25 extend from
the second major surface 24 into the needle support layer 5 for
accommodating the first membrane 15 therein during pressurising of the
corresponding active substance chambers 4 as will be described below. The
membrane accommodating recesses 25 are disposed in a matrix which is
similar to the matrix in which the micro-needles 6 are disposed and are
aligned with the micro-needles 6, and in turn are aligned with
corresponding ones of the active substance chambers 4 in the active
substance layer 3.

[0142] The micro-needles 6 are of conical shape of circular transverse
cross-section, and each micro-needle 6 defines a longitudinally extending
central axis 26 and terminates in a distal pointed tip 27 for penetrating
the skin of the subject. A communicating means, namely, a communicating
bore 28 extends through each micro-needle 6 from the corresponding
membrane accommodating recess 25 for accommodating the active substance 2
therethrough from the corresponding active substance chamber 4. Each
communicating bore 28 defines a first portion 29 which extends through
the needle support layer 5 from the corresponding membrane accommodating
recess 25, and a second portion 30 which extends from the first portion
29 through the corresponding micro-needle 6. The communicating bore 28
extends through the corresponding micro-needle 6 parallel to the central
axis 26 but spaced apart therefrom so that the second portion 30 of each
communicating bore 29 terminates in an outlet 31 in an outer surface 32
of the micro-needle 6 at a location spaced apart from the distal tip 27.
By offsetting the communicating bore 28 from the central axis 26, so that
the communicating bore 28 does not extend through the distal tip 27,
coring in the micro-needles 6 is avoided. Coring is caused by a core of
tissue being engaged by a communicating bore as the micro-needle is
penetrating the skin of the subject. The tissue core in general blocks
the communicating bore. In this embodiment of the invention the
micro-needles 6 are of sufficient length to penetrate and extend through
the stratum corneum.

[0143] The first membrane 15 is sealably secured to the first major
surface 20 of the active substance layer 3 for sealably closing the
active substance chambers 4 adjacent the first major surface 20, and for
isolating the active substance chambers 4 from the communicating bores 28
of the corresponding micro-needles 6. Sealably securing the first
membrane 15 to the first major surface 20 of the active substance layer 3
prevents leakage of the active substance 2 from one active substance
chamber 4 to adjacent active substance chambers 4. The first membrane 15
is also sealably secured to the second major surface 24 of the needle
support layer 5 in order to prevent leakage of the active substance from
one membrane accommodating recess 25 to adjacent membrane accommodating
recesses 25 as the active substance is being delivered to the subject.
The first membrane 15, which is impermeable to the active substance 2, is
of a burstable material which also has limited stretching properties.
Such a burstable material may be provided by a thin film plastics sheet
material, for example, a polymer film material, or by a foil, such as a
metal foil which may be laminated with a thin plastics film.

[0144] A puncturing means comprising a plurality of puncturing members 33
integrally formed with the needle support layer 5 are located in the
needle support layer 5 and extend therefrom into the corresponding ones
of the membrane accommodating recesses 25. Each puncturing member 33
extends from the needle support layer 5 towards the first membrane 15 and
terminates in a piercing means, namely, a piercing point 35 for piercing,
and in turn puncturing and bursting the first membrane 15 for
communicating the communicating bore 28 of the corresponding micro-needle
6 with the corresponding active substance chamber 4.

[0145] Each puncturing member 33 terminates in the corresponding piercing
point 35 within the corresponding membrane accommodating recess 25 spaced
apart a distance d from a plane defined by the second major surface 24 of
the needle support layer 5, and in turn spaced apart the distance d from
the first membrane 15. Accordingly, when pressure is applied to the
active substance in the corresponding one of the active substance
chambers 4, the pressure of the active substance 2 on the first membrane
15 causes the first membrane 15 to expand and balloon into the
corresponding membrane accommodating recess 25 as illustrated in FIG. 4.
As the pressure of the active substance acting on the first membrane 15
increases, the amount by which the first membrane 15 extends and balloons
into the membrane accommodating recess 25 progressively increases, until
the first membrane 15 engages the piercing point 35 of the puncturing
member 33, thus puncturing, and in turn bursting, and in general,
rupturing the first membrane 15 for communicating the communicating bore
28 of the corresponding micro-needle 6 with the corresponding one of the
active substance chambers 4.

[0146] By setting the distance d by which the piercing point 35 of each
puncturing member 33 is spaced apart from the plane defined by the second
major surface 24 of the needle support layer 5 and in turn from the first
membrane 15, the pressure of the active substance 2 in the corresponding
active substance chamber 4 at which bursting of the first membrane 15
takes place can be relatively accurately set. Once the first membrane 15
bursts, the active substance 2 is delivered from the corresponding active
substance chamber 4 at the pressure of the active substance at which the
first membrane 15 bursts. Therefore, the pressure at which the active
substance 2 is delivered from the active substance chambers 4 to the
subject can be determined by setting the distance d by which the piercing
points 35 of the puncturing members 33 are spaced apart from the second
major surface 24 of the needle support layer 5, and in turn from the
first membrane 15.

[0147] By setting the pressure of the active substance at which the first
membrane bursts, the velocity at which the active substance 2 is injected
into the subject through the communicating bore 28 of each micro-needle 6
from the corresponding active substance chamber 4 can be determined, and
thus set at a target injection velocity value. By setting the injection
velocity at which the active substance is delivered into the subject from
each micro-needle at a desired target injection velocity value, the depth
below the skin of the subject to which the active substance is delivered
can likewise be set at a desired depth. By virtue of the fact that the
micro-needles 6 extend through the stratum corneum, any resistance which
would have been offered to the active substance as it passed through the
stratum corneum is avoided, and thereby by setting the injection velocity
at a predetermined target injection velocity allows the depth to which
the active substance is injected below the skin of the subject to be
relatively accurately determined.

[0148] In this embodiment of the invention each puncturing member 33 is
centrally located on the central axis 26 of the corresponding
micro-needle 6 and is also centrally located in the corresponding
membrane accommodating recess 25, so that the piercing point 35 engages
the first membrane 15 at its point of maximum travel from a plane defined
by the second major surface 24 of the needle support layer 5 when the
corresponding active substance chamber 4 is pressurised to a predefined
pressure. By locating the piercing point 35 of the puncturing member 33
at the position of maximum travel of the first membrane 15 increases the
resolution and the reliability at which the pressure of the active
substance at which the first membrane bursts can be set.

[0149] By being able to set the pressure at which the active substance 2
is delivered to the subject, a major advantage of the micro-needle device
1 according to the invention is achieved, which is discussed above and as
is discussed in more detail below.

[0150] The drive substance layer 9 is also of a polymer material and
defines a first face, namely, a first major surface 37, and a second
face, namely, an opposite second major surface 38. The drive substance
chambers 10 are formed by cylindrical bores of diameter similar to the
diameter of the active substance chambers 4 and extend through the drive
substance layer 9 from the first surface 37 to the second surface 38. The
drive substance chambers 10 are disposed in a matrix similar to the
matrix in which the active substance chambers 4 are disposed, and are
aligned with the active substance chambers 4. The drive substance 11
which is provided in the drive substance chambers 10, in this embodiment
of the invention is an expandable material which comprises a plurality of
gas-filled polymer micro-spheres of the type which are sold under the
Trade Mark EXPANCEL, and which are expandable in response to being
heated.

[0151] The second membrane 16, which is impermeable to the active
substance and the drive substance, comprises a stretchable material,
which in this embodiment of the invention is a stretchable polymer
material, and is sealably secured to the second major surface 21 of the
active substance layer 3 for sealably closing the active substance
chambers 4 adjacent the second major surface 21. The second membrane 16
is also sealably secured to the first major surface 37 of the drive
substance layer 9 in order to sealably close the drive substance chambers
10 adjacent the first major surface 37 thereof. The stretchable material
of the second membrane 16 is such as to permit the second membrane 16, on
expansion of the drive substance 11 in the drive substance chambers 10,
to expand into the corresponding active substance chambers 4 to almost
fully define the corresponding active substance chambers 4 in order to
pressurise and to substantially fully discharge the active substance from
the corresponding active substance chambers 4. The second membrane 16 is
illustrated in FIG. 4 in a configuration which substantially fully
defines the corresponding active substance chamber 4 for pressurising and
discharging the active substance 11 therefrom.

[0152] A barrier means, in this embodiment of the invention a perforated
barrier panel 40, which is formed by a grating 41 or a grill, is located
in each active substance chamber 4 adjacent the first major surface 20 of
the active substance layer 3 to prevent the second membrane 16 extending
beyond the corresponding active substance chamber 4 into the
corresponding membrane accommodating recess 25. By preventing the second
membranes 16 extending into the membrane accommodating recesses 25,
puncturing of the second membrane 16 by the puncturing member 33 is
avoided, and in turn contamination of the active substance with the drive
substance is also avoided. Openings 42 in the grating 41 are sized to
accommodate the active substance 2 therethrough from the active substance
chamber 4 to the communicating bore 28 of the corresponding micro-needle
6. Thus, the barrier panel 40 is permeable to the active substance 2.
However, the openings 42 in the grating 41 are of a size so that the
barrier panel 40 acts as a barrier to the second membrane 16 passing
therethrough into the corresponding membrane accommodating recess 25. In
this embodiment of the invention the barrier panels 40 in the respective
active substance chambers 4 are of polymer material and are formed
integrally with the active substance layer 3 by perforated portions of
the active substance layer 3 extending across the active substance
chambers 4 adjacent the first major surface 20 of the active substance
layer 3.

[0153] The activation layer 12 defines a first face, namely, a first major
surface 45, and a second face, namely, an opposite second major surface
46. The activation layer 12 is of a substrate material which is suitable
for facilitating the formation of a printed circuit thereon, although the
activation layer 12 may be of any other suitable material, such as a
polymer material, a ceramics material or any other suitable material.

[0154] The heating elements 14 are formed on the first major surface 45,
and are disposed in a matrix which is similar to the matrix in which the
active substance chambers 4 are disposed, and are thus aligned with the
corresponding ones of the drive substance chambers 10 for heating the
drive substance 11 therein. The heating elements 14 may be formed by
electrically resistive elements, such as thick film resistors formed on
the substrate forming the activation layer 12 or on a ceramics layer
which would also form the activation layer 12. The heating elements 14
are independently addressable, in order to be independently operable so
that the drive substance 11 in the drive substance chambers 10 are
independently expandable, for in turn independently discharging the
active substance 2 from each active substance chamber 4. Electrical
circuitry (not shown) is formed on the first major surface 45 of the
substrate of the activation layer 12 for facilitating the independent
addressing of the heating elements 14. Such an arrangement of heating
elements 14 on an activation layer 12 is described in PCT Published
Application Specification No. WO 2009/069112 of the present applicant. A
programmable microcontroller or microprocessor (neither of which are
shown) may be formed in the activation layer 12 or adapted to be secured
thereto for controlling the operation of the heating elements 14 as will
be described below.

[0155] The third membrane 17, which is impermeable to the drive substance,
is of a heat insulating material and is sealably secured to the second
major surface 38 of the drive substance layer 9 for sealably closing the
drive substance chambers 10 adjacent the second major surface 38 of the
drive substance layer 9. The third membrane 17 is also sealably secured
to the activation layer 12 adjacent the first major surface 45. Openings
47 which correspond with the respective drive substance chambers 10
extend through the third membrane 17 and are sealably closed by heat
conductive closure discs 48, typically of a metal material for conducting
heat from the heating elements 14 to the corresponding drive substance
chamber 10. In this embodiment of the invention the openings 47 are
circular, as are the closure discs 48. By providing the third membrane 17
of a heat insulating material, the heat generated by each heating element
14 is directed substantially solely into the drive substance 11 in the
corresponding drive substance chamber 10.

[0156] Typically, the layers 3, 5, 9 and 12 with the membranes 15, 16 and
17 located therebetween will be tightly clamped together and the layers
3, 5, 9 and 12 will be ultrasonically welded adjacent their respective
peripheral edges in order to retain the assembly of the layers 3, 5, 9
and 12 with the membranes 15, 16 and 17 located therebetween tightly and
sealably secured together. Alternatively, the assembly of the layers 3,
5, 9 and 12 with the membranes 15, 16 and 17 may be sealably clamped
together in a suitable housing. Although not illustrated, alignment
means, such as alignment pins may be provided extending from the layers
3, 5, 9 and 12, which would extend through corresponding openings in the
corresponding membranes 15, 16 and 17 and which would engage
corresponding recesses in the adjacent ones of the layers 3, 5, 9 and 12
may be provided for aligning the layers 3, 5, 9 and 12 with the
micro-needles 6, the active substance chambers 4, the drive substance
chambers 9 and the heating elements 14 correspondingly aligned with each
other.

[0157] A means for securing the micro-needle device 1 to the skin of a
subject comprises an adhesive patch 49, which is secured to the second
major surface 46 of the activation layer 12. A peripheral portion 50 of
the patch 49 extends around the periphery of the activation layer 12 for
bonding the micro-needle device 1 to the skin of a subject.
Alternatively, a strap (not shown) secured to the activation layer 12 may
be provided for securing the micro-needle device 1 to the subject. In
cases where the layers 3, 5, 9 and 12 with the membranes 15, 16 and 17
therebetween are located in a housing, the adhesive patch 49 or the strap
would be secured to the housing. In general, where the micro-needle
device 1 is provided for securing to a site of the subject where it is
not feasible to secure the micro-needle device 1 with a strap, the
micro-needle device 1 is secured with the adhesive patch 49. However,
where the micro-needle device 1 is to be secured to a site on the arm or
a leg of a subject, the micro-needle device 1 would more typically be
provided with a strap which could extend around the arm or leg of the
subject and would be secured by a suitable securing means, for example, a
buckle, hooks and loops which are sold under the Trade Mark VELCRO or
other suitable securing means. On the other hand, where the site is
unsuitable for use of a strap to secure the micro-needle device 1 to a
site on a subject, the micro-needle device 1 is secured by the patch 49.

[0158] In this embodiment of the invention the active substance layer 3 is
of thickness of approximately 1.6 mm, and may range in thickness from 0.2
mm to 3.0 mm. The drive substance layer 9 is of thickness of
approximately 1.5 mm and may range in thickness from 0.5 mm to 3.0 mm.
The active substance chambers 4 and the drive substance chambers 10 are
of similar diameter of 2.0 mm, and may range in diameter from 0.5 mm to
10 mm. The needle support layer 5 is of thickness of approximately 0.6 mm
and may range in thickness from 0.2 mm to 1.0 mm. The micro-needles 6 are
of length of approximately 1.0 mm, and may range in length from 0.3 mm to
3.0 mm. The diameter of each micro-needle 6 adjacent the first major
surface 23 of the needle support layer 5 is approximately 0.6 mm, and may
range in diameter from 0.2 mm to 1.0 mm. The depth of each membrane
accommodating recess 25 is approximately 0.3 from the plane defined by
the second major surface 24 of the needle support layer 5 and may range
in depth from 0.1 mm to 0.8 mm.

[0159] The distance d of the piercing tip 35 of the puncturing member 33
from the plane defined by the second major surface 24 of the needle
support layer 5 will be dependent on the pressure of the active substance
2 in the corresponding active substance chamber 4 at which the first
membrane 15 is to burst, and will also be dependent on the stretch
characteristics of the first membrane 15. However, in general, it is
envisaged that the distance d between the piercing point 35 of the
puncturing member 33 from the plane defined by the second major surface
24 of the needle support layer 5 will be in the range of 100 microns to
600 microns.

[0160] Typically, the first membrane 15 will be of thickness of the order
of 5 to 50 microns, the second membrane 16 will be of thickness of the
order of 5 to 50 microns and the third membrane 17 will be of thickness
of the order of 5 to 50 microns.

[0161] In this embodiment of the invention the number of active substance
chambers 4 is thirty-six and are arranged in a matrix of six by six.
Since the number of drive substance chambers 10 and the number of heating
elements 14 and the number of micro-needles 6 is similar to the number of
active substance chambers, the micro-needle device 1 comprises 36
micro-needles, 36 drive substance chambers 10, thirty-six heating
elements 14 arranged in similar six by six matrices as the six by six
matrix of active substance chambers 4.

[0162] Returning now to the advantage of setting of the pressure at which
the active substance is injected into a subject from the respective
active substance chambers 4, as discussed above, by setting the pressure
of the active substance 2 at which the first membrane 15 bursts allows
the depth beneath the skin of the subject to which the active substance
is delivered either intradermally, transdermally, subcutaneously or
intramuscularly to the subject to be set. The depth beneath the skin of a
subject to which the active substance is delivered is a function of the
velocity of the active substance as it exits the outlet 31 of the
communicating bore 28 of the corresponding micro-needle 6. The exit
velocity of the active substance is a function of the pressure at which
the active substance 2 is delivered from the corresponding active
substance chamber 4. Thus, the greater the pressure at which the active
substance 2 is delivered from the active substance chamber 4, the greater
will be the depth beneath the skin of a subject to which the active
substance will be delivered.

[0163] It is known to use needle-free jet injectors for delivering an
active substance transdermally, to a subject, and further it is known
that by increasing the pressure at which the active substance is
delivered to the subject, the depth beneath the skin of the subject to
which the active substance is delivered is increased. However, a problem
with this known method using needle-free jet injectors is that the jet of
active substance must first penetrate the stratum corneum of the subject.
The stratum corneum varies in strength and depth from subject to subject,
due to many variables, for example, the age of the subject, the race of
the subject, the location in the body of the subject at which the active
substance is to be delivered, and the humidity of the environment in
which the subject is present during an injection of the active substance.
Thus, without knowing the exact strength and depth of the stratum corneum
at the precise time at which the active substance is to be delivered by a
needle-free jet injector, the depth to which the active substance is
delivered intradermally, transdermally, subcutaneously or intramuscularly
to a subject cannot be accurately controlled.

[0164] However, in the micro-needle device 1 according to the invention,
the micro-needles 6 being of sufficient length to extend through the
stratum corneum are also of sufficient length so that the outlets 31 from
the communicating bores 28 of the micro-needles 6 clear the stratum
corneum, and therefore the active substance is to accommodated through
the micro-needles 6 past the stratum corneum. Accordingly, by accurately
setting the pressure at which the first membrane 15 bursts, the pressure
at which the active substance 2 is delivered to the subject, and in turn
the injection velocity of the active substance is delivered to the
subject is accurately set. Thus, the depth to which the active substance
2 is delivered beneath the skin of the subject can likewise be accurately
set, since the stratum corneum has been bypassed by the micro-needles 6
of the micro-needle device 1.

[0165] Accordingly, to increase the pressure of the active substance in
the active substance chambers 4 at which the first membrane 15 bursts
requires setting the distance d of the piercing points 35 of the
puncturing members 33 at a greater distance from the plane defined by the
second major surface 24 of the needle support layer 5. Thus, prior to
manufacture of the needle support layer 5, the distance d by which the
piercing points 35 of the puncturing members 33 is spaced apart from the
plane defined by the second major surface 24 of the needle support layer
5 may be set in order to determine the pressure of the active substance
in the corresponding active substance chambers 4 at which the first
membrane 15 is to burst. It will be appreciated that the distance d
between the piercing points 35 of the puncturing members 33 from the
plane defined by the second major surface 24 of the needle support layer
5 may be different from membrane accommodating recess 25 to membrane
accommodating recess 25.

[0166] By locating each puncturing member 33 and in turn the piercing
point 35 thereof centrally in the corresponding membrane accommodating
recess 25 on the central axis 26 of the corresponding micro-needle 6, the
resolution and in turn the reliability with which the pressure at which
the first membrane 15 bursts can be set is maximised. This is due to the
fact that the distance of travel of the first membrane 15 from the plane
defined by the second major surface 24 of the needle support layer 5 per
unit of increase in pressure of the active substance 2 in the
corresponding active substance chamber 4 is greatest along the central
axis 26 of the corresponding micro-needle 6, which coincides with the
centre of the membrane accommodating recess 25.

[0167] In use, the needle support layer 5 is produced with the piercing
points 35 of the puncturing members 33 at the appropriate distance d from
the plane defined by the second major surface 24 of the needle support
layer 5. Where the micro-needle device 1 is required to deliver one or
more active substances to the same depth beneath the skin of the subject,
the distance d of the piercing points 35 of the puncturing members 33
from the plane defined by the second major surface 24 of the needle
support layer 5 will be similar. However, where the active substance or
active substances are to be delivered to different depths beneath the
skin of the subject, the distance d of the piercing points 35 of the
puncturing members 33 from the plane defined by the second major surface
24 of the needle support layer 5 will be different from puncturing member
33 to puncturing member 33 and will be set depending on the depth beneath
the skin of the subject to which the active substance or substances in
the corresponding active substance chamber 4 or chambers 4 are to be
delivered to the subject.

[0168] Typically, in assembling the micro-needle device 1, the second
membrane 16 is sealably secured to the second major surface 21 of the
active substance layer 3 to sealably close the active substance chambers
4 adjacent the second major surface 21. The active substance chambers 4
are then charged with the active substance or active substances,
depending on whether the micro-needle device 1 is to be provided to
deliver one type of active substance or different types of active
substances to a subject. The first membrane 15 is then sealably secured
to the first major surface 20 of the active substance layer 3 in order to
sealably retain the active substance or the active substances in the
active substance chambers 4.

[0169] The third membrane 17 with the closure discs 48 sealably located in
the openings 47 is then sealably secured to the second major surface 38
of the drive substance layer 9, and the drive substance chambers 10 are
charged with the drive substance 11. The drive substance layer 9 is then
secured to the active substance layer 3 by sealably securing the first
major surface 37 of the drive substance layer 9 to the second membrane
16. The activation layer 12 with the adhesive patch 49 secured to the
second major surface 46 is secured to the assembled active substance
layer 3 and the drive substance layer 9 by securing the activation layer
12 to the third membrane 17.

[0170] The needle support layer 5 is then secured to the assembled active
substance layer 3, the drive substance layer 9 and the activation layer
12 by sealably securing the second major surface 24 of the needle support
layer 5 to the first membrane 15.

[0171] During assembly of the needle support layer 5, the active substance
layer 3, the drive substance layer 9 and the activation layer 12, the
active substance chambers 4 are aligned with the corresponding drive
substance chambers 9, which in turn are aligned with the heating elements
14, and the micro-needles 6 are aligned with the active substance
chambers 4, so that corresponding ones of the micro-needles 6, the active
substance chambers 4, the drive substance chambers 9 and the heating
elements 14 are appropriately aligned with each other.

[0172] Typically the first, second and third membranes 15, 16 and 17 are
sealably secured to the corresponding ones of the needle support layer 5,
the active substance layer 3, and the drive substance layer 9 by
ultrasonic welding, although the membranes 15, 16 and 17 may be sealably
secured to the layers 3, 5 and 9 by a suitable adhesive. However, it
should be noted that the first membrane 15 is not secured or bonded to
the barrier panels 40 in the active substance layer 3, in order to
facilitate ballooning of the first membrane 15 into the respective
membrane accommodating recesses 25.

[0173] Prior to securing the micro-needle device 1 to the subject, the
microprocessor (not shown), which as discussed above, may be incorporated
in the activation layer 12 or secured thereto, is programmed to dispense
the active substance or the active substances to the subject in
accordance with a suitable treatment regime. For example, the
microprocessor could be programmed to provide a treatment regime over a
five- or a seven-day period. Where the micro-needle device is adapted to
administer only one active substance to a subject, programming of the
microprocessor (not shown) requires selecting the appropriate number of
heating elements to be activated in order to produce a dose of the active
substance of the appropriate volume. In other words, the microprocessor
is programmed so that the appropriate number of heating elements are
activated to pressurise the active substance 2 in an appropriate number
of the active substance chambers 4 to produce a dose of the active
substance of the required volume. Programming of the microprocessor also
requires inputting the number of doses to be administered to the subject
per day, and the times during the day or night at which the doses are to
be administered to the subject. Once programmed, the micro-needle device
is ready to be attached to the subject.

[0174] Where the micro-needle device 1 is adapted to deliver more than one
active substance to a subject, programming requires inputting of the
number of heating elements to be activated to produce doses of the
respective active substances, and also the times of the day or night at
which the doses of the respective active substances are to be
administered to the subject.

[0175] The micro-needle device 1 may also be used to provide a treatment
regime over a much shorter time duration, for example, a half hour
period, a one hour period, a half day period, a one or a two day period
as desired.

[0176] With the micro-needle device 1 appropriately programmed and secured
to an appropriate site on the subject with the micro-needles 6
penetrating through the stratum corneum of the subject, and with the
outlets 31 of the communicating bores 28 clear of the stratum corneum, on
activation of one or more of the heating elements 14, the drive substance
11 in the corresponding drive substance chambers 10 expands, thereby
urging the second membrane 16 into corresponding ones of the active
substance chambers 4 to pressurise the active substance 2 therein. The
rising pressure of the active substance 2 in the active substance
chambers 4 urges the first membrane 15 to balloon into the corresponding
membrane accommodating recesses 25. On the pressure of the active
substance in the active substance chambers 4 being at the set pressure at
which the active substance is to be delivered to the subject, the
ballooning first membrane 15 engages the piercing points 35 of the
puncturing members 33 in the corresponding membrane accommodating
recesses 25. The first membrane 15 is then punctured and bursts, thereby
communicating the active substance chambers 4 with the communicating
bores 28 of the corresponding micro-needles 6, which correspond with the
heating elements 14 which have been activated. On bursting of the first
membrane 15, the second membrane 16 is urged further into the
corresponding active substance chamber 4, thus maintaining the pressure
on the active substance in the active substance chamber 4 at the desired
set pressure, and the active substance is delivered from the active
substance chamber 4 at the set pressure, and in turn at the target
injection velocity, by the action of the second membrane 16 continuing to
expand into the active substance chamber 4 under the action of the drive
substance in the corresponding drive substance chamber 10.

[0177] During the treatment period during which the subject is to be
subjected to the treatment regime, the appropriate ones of the heating
elements 14 are activated at the appropriate times in order to administer
respective doses of the active substance or active substances of the
appropriate volume at the appropriate times over the five- to seven-day
period of the treatment regime. However, in certain cases, it is
envisaged that each active substance chamber 4 may comprise an
appropriate amount of the active substance to constitute one dose of the
active substance, and in which case, only one heating element 14 will be
activated in order to administer a dose of the active substance to the
subject.

[0178] Referring now to FIG. 6, there is illustrated a portion of an
active substance cartridge according to the invention, indicated
generally by the reference numeral 60, for use with a micro-needle device
substantially similar to the micro-needle device 1 described with
reference to FIGS. 1 to 5. In this embodiment of the invention the active
substance cartridge 60 comprises an active substance cartridge element 61
which is formed by an active substance layer 62 which is similar to the
active substance layer 3 of the micro-needle device 1, and similar
components are identified by the same reference numerals. The active
substance layer 62 comprises a plurality of active substance chambers 4
disposed in a matrix, and extending from a second major surface 21 of the
active substance layer 62 and terminating adjacent a first major surface
20 of the active substance layer 62 in a barrier panel 40 provided by a
grating 41. For ease of illustration only one active substance chamber 4
is illustrated. A first membrane 63 which is similar to the first
membrane 15 of the micro-needle device 1 is sealably secured to the first
major surface 20 of the active substance layer 62 for sealably closing
the active substance chambers 4 adjacent the first major surface 20, but
is not secured to the barrier panel 40. A second membrane 64 of a
stretchable material, which is similar to the second membrane 16 of the
micro-needle device 1 is sealably secured to the second major surface 21
of the active substance layer 62 for sealably closing the active
substance chambers 4 adjacent the second major surface 21.

[0179] The grating 41 is similar to the grating 41 of the micro-needle
device 1, and is formed in each active substance chamber 4 adjacent the
first major surface 20 of the active substance layer 62 for accommodating
the active substance therethrough, and for preventing travel of the
second membrane 64 past the grating 41.

[0180] Otherwise, the active substance cartridge 60 is similar to the
active substance layer 3 when the first membrane 15 and the second
membrane 16 are sealably secured to the active substance layer 3 of the
micro-needle device 1.

[0181] In use, the active substance cartridge 60 will be pre-charged with
the active substance. In general, after one of the first membrane 63 and
the second membrane 64 has been sealably secured to the active substance
layer 62, the active substance chambers 4 will be charged with the one or
more active substances, and then the other of the first and second
membranes 63 and 64 will be sealably secured to the active substance
layer 62. It is envisaged that the active substance cartridge 60 would be
sold separately to be subsequently secured to a needle support layer 5
and a drive substance layer 9 by, for example, a doctor, a paramedic or
the like.

[0182] Additionally, it is envisaged that the drive substance layer could
be provided as drive substance cartridge with the drive substance
chambers thereof already charged with the drive substance. The drive
substance cartridge would be provided with a third membrane similar to
the third membrane 17 sealably secured to the second major surface 38 of
the drive substance layer, and a second membrane, similar to the second
membrane 16 would be sealably secured to the first major surface 37 of
the drive substance layer 9. Thus, in this case the micro-needle device
when assembled with the active substance cartridge 60 according to the
invention and a drive substance cartridge pre-charged with the driving
substance, two second membranes would be provided between the active
substance layer 62 and the drive substance layer, which would be secured
together, one second membrane being sealably secured to the first major
surface 37 of the drive substance layer 9, and the other second membrane
being secured to the second major surface 21 of the active substance
layer 62. Both second membranes would be sufficiently stretchable to
stretch into the corresponding active substance chambers 4 to
substantially define the active substance chambers 4 as illustrated and
described with reference to FIG. 4.

[0183] Alternatively, it is envisaged that the second membrane which would
be secured to the second major surface 21 of the active substance layer
62 may be provided as a burstable membrane, which on being subjected to
pressure from the second stretchable membrane which would be attached to
the first major surface 37 of the drive substance layer 9 would burst,
thus allowing the second stretchable membrane 16 which would be attached
to the first major surface 37 of the drive substance layer 9 to expand
into the corresponding active substance chamber 4 in the active substance
layer 62 to substantially define the active substance chambers 4.

[0184] Referring now to FIGS. 7 and 8, there is illustrated a portion of a
micro-needle device also according to the invention and indicated
generally be reference numeral 65. The micro-needle device 65 is
assembled from the active substance cartridge 60 described with reference
to FIG. 6. The micro-needle device 65 is substantially similar to the
micro-needle device 1 and similar components are identified by the same
reference numerals. In this embodiment of the invention the active
substance cartridge is provided with a first membrane 62 of a burstable
polymer film material, and a second membrane 64 also of a burstable
polymer film material. The second stretchable membrane 16 which is
secured to the first major surface 37 of the drive substance layer 9 is
of a similar stretchable material to that of the second membrane 16 of
the first micro-needle device 1. Thus, as illustrated in FIG. 8, on
activation of the heating elements 14 of the activation layer 12, the
drive substance in the corresponding drive substance chambers 10 expands,
thus urging the second stretchable membrane 16 which is secured to the
drive substance layer 9 against the second burstable membrane 64, which
is secured to the second major surface 21 of the active substance layer
62. The action of the second stretchable membrane 16 on the second
burstable membrane 64 bursts the second membrane 64. This in turn allows
the second stretchable membrane 16 to be urged into the corresponding
active substance chambers 4 by the drive substance in the corresponding
drive substance chambers 10, so that the second stretchable membrane 16
substantially defines the corresponding active substance chambers 4 for
urging the active substance therefrom.

[0185] Referring now to FIGS. 9 and 10, there is illustrated a portion 70
of an active substance layer 71 of a micro-needle device according to
another embodiment of the invention. The active substance layer 71 in
this embodiment of the invention is similar to the active substance layer
3 of the micro-needle device 1, as is the micro-needle device
substantially similar to the micro-needle device 1, and similar
components are identified by the same reference numerals. The main
difference between the active substance layer 71 of this embodiment of
the invention and that of the micro-needle device 1 described with
reference to FIGS. 1 to 5 is in the perforated barrier panel 40. In this
embodiment of the invention the barrier panel 40 is provided by a
plurality of members 72 radiating outwardly from a central axis defined
by the corresponding active substance chamber 4 so that the radial
members 72 define active substance accommodating openings 73 for
accommodating the active substance from the active substance chamber 4 to
the communicating bore of the corresponding micro-needle.

[0186] Referring now to FIGS. 11 to 13, there is illustrated a portion of
a micro-needle device according to a further embodiment of the invention
indicated generally by the reference numeral 75. The micro-needle device
75 is substantially similar to the micro-needle device 1 and similar
components are identified by the same reference numerals. The main
difference between the micro-needle device 75 and the micro-needle device
1 is that a means for effecting a seal between the first membrane 15 and
the active substance layer 3 and the needle support layer 5 is provided.
Additionally, a means for effecting a seal between the second membrane 16
and the active substance layer 3 and the drive substance layer 9 is
provided, as is a means for effecting a seal between the drive substance
layer 9 and the third membrane 17.

[0187] Each means for effecting the seal comprises an annular ridge type
projecting element 76 extending from the corresponding one of the first
and second major surfaces 20 and 21 of the active substance layer 3, the
first and second major surfaces 37 and 38 of the drive substance layer 9,
and from the second major surface 24 of the needle support layer 5. The
annular projecting elements 76 extend around the corresponding ones of
the active substance chambers 4, the drive substance chambers 10 and the
membrane accommodating recesses 25 for sealably engaging the
corresponding one of the first, second and third membranes 15, 16 and 17.
Each annular projecting element 76 is of substantially semi-circular
transverse cross-section and terminates in a radiused membrane abutting
convex surface 77 for sealably abutting and engaging the adjacent one of
the first, second and third membranes 16, 16 and 17.

[0188] The annular projecting elements 76 extending from the first major
surface 20 of the active substance layer 3 and from the second major
surface 24 of the needle support layer 5 co-operate with each other for
sealably engaging and entrapping the first membrane 15 therebetween in
order to sealably close the corresponding active substance chamber 4
adjacent the first major surface 20 of the active substance layer 3,
thereby preventing leakage of active substance from one active substance
chamber 4 to adjacent active substance chambers 4. The co-operating
action of the annular projecting elements 76 on the first and second
major surfaces 20 and 24 of the active substance layer 3 and the needle
support layer 5, respectively, also prevents leakage of the active
substance from one membrane accommodating recess 25 to adjacent ones of
the memory accommodating recesses 25 during delivery of the active
substance from the corresponding active substance chamber 4 through the
corresponding micro-needle 6.

[0189] The annular projecting elements 76 extending from the second major
surface 21 of the active substance layer 3 and from the first major
surface 37 of the drive substance layer 9 co-operate with each other and
sealably engage and trap the second membrane 16 therebetween for sealably
closing the corresponding active substance chamber 4 and the
corresponding drive substance chamber 10. The annular projecting elements
76 which extend from the second major surface 38 of the drive substance
layer 9 co-operate with the first major surface 45 of the activation
layer 12 for sealably engaging the third membrane 17 for in turn sealably
closing the corresponding drive substance chamber 10.

[0190] In this embodiment of the invention the micro-needle device 75 is
assembled in a similar manner as that of the micro-needle device 1, with
the first membrane 15 located between the active substance layer 3 and
the needle support layer 5, the second membrane 16 located between the
active substance layer 3 and the drive substance layer 9, and the third
membrane 17 located between the drive substance layer 9 and the
activation layer 12. However, in this embodiment of the invention the
assembly of the needle support layer 5, the active substance layer 3, the
drive substance layer 9 and the activation layer 12 and the first, second
and third membranes 15, 16 and 17 are held together by a suitable
clamping arrangement which clamps the layers 3, 5, 9 and 12 tightly with
the membranes 15 to 17 therebetween and with the annular projecting
elements 76 tightly engaging the first, second and third membranes 15, 16
and 17 therebetween. The clamped assembly is then located in a frame or
in a housing. Alternatively, the layers 3, 5, 9 and 12 with the membranes
15, 16 and 17 therebetween are ultrasonically welded together adjacent
peripheral edges thereof.

[0191] The advantage of providing the annular projecting elements 76 on
the second major surface 24 of the needle support layer 5, on the first
and second major surfaces 20 and 21 of the active substance layer 3 and
on the first and second major surfaces 37 and 38 of the drive substance
layer 9 is that a good annular seal is effected between the corresponding
layer 3, 5, 9 and 12 and the adjacent ones of the first, second and third
membranes 15, 16 and 17 around the active substance chambers 4 and the
drive substance chambers 10. The seal extends completely around the
corresponding adjacent one of the active substance chamber 4 and the
drive substance chamber 10, as well as and around the adjacent
corresponding membrane accommodating recess 25, thereby preventing
leakage of the active substance or the driving substance from the
corresponding active and drive substance chambers 4 and 10 to adjacent
active and drive substance chambers 4 and 10, and from the membrane
accommodating recesses 25 to adjacent membrane accommodating recesses 25.

[0192] It is envisaged that in some embodiments of the invention the seal
between the first membrane 15 and the active substance layer 3 and the
needle support layer 5 may be achieved by annular projecting elements 76
extending from one of the first major surface 20 of the active substance
layer 3 and the second major surface 24 of the needle support layer 5,
and in which case, the annular projecting elements 76 would engage the
first membrane 15 and co-operate with the other of the first major
surface 20 and the second major surface 24 of the active substance layer
3 and the drive substance layer 9, respectively, for effecting the seal
between the first membrane 15 and the respective active substance layer 3
and the needle support layer 5. In cases where annular projecting
elements 76 are provided extending from only one of the first major
surface 20 of the active substance layer 3 and the second major surface
24 of the needle support layer 5, it is envisaged that the annular
projecting elements 76 will extend from the second major surface 24 of
the needle support layer 5.

[0193] Similarly, it is envisaged that in certain cases, annular
projecting elements 76 may be provided extending from only one of the
second major surface 21 of the active substance layer 3 and the first
major surface 37 of the drive substance layer 9 for engaging the second
membrane 16, and in which case, it is envisaged that the annular
projecting elements 76 will extend from the first major surface 37 of the
drive substance layer 9.

[0194] Referring now to FIG. 14, there is illustrated a portion of a
micro-needle device according to another embodiment of the invention,
indicated generally by the reference numeral 80. The micro-needle device
80 is substantially similar to the micro-needle device 1 and similar
components are identified by the same reference numerals. The main
difference between the micro-needle device 80 and the micro-needle device
1 is that a means for effecting a seal between the first membrane 15 and
the active substance layer 3 and the needle support layer 5 is provided,
and a means for effecting a seal between the second membrane 16 and the
active substance layer 3 and the drive substance layer 9 is also
provided. In this embodiment of the invention the seal effecting means
comprise pairs of interengageable complementary formations on the
respective layers 3, 5 and 9. The pairs of interengageable complementary
formations also act as alignment means for aligning the active substance
layer 3 with the needle support layer 5 and the drive substance layer 9,
so that the corresponding ones of the active and drive substance chambers
4 and 10 and the corresponding membrane accommodating recesses 25 are
appropriately aligned with each other.

[0195] One of each pair of interengageable complementary formations
comprising an annular alignment projecting element 81 extending from the
corresponding one of first major surfaces 20 and 37 of the active
substance layer 3 and the drive substance layer 9, respectively, which
engages a corresponding alignment recess 82 formed in the corresponding
one of second major surface 24 of the needle support layer 5 and in the
second major surface 21 of the second layer 3. The alignment elements 81
extend around corresponding ones of the active and drive substance
chambers 4 and 10, while the alignment recesses 82 extend around and into
the corresponding ones of the membrane accommodating recesses 25 and the
active substance chambers 4. The outer diameter of the alignment elements
81 and the inner diameter of the alignment recesses 82 are such as to
accommodate the first and second membranes 15 and 16 therebetween when
the needle support layer 5, the active substance layer 3 and the drive
substance layer 9 are assembled together with the first and second
membranes 15 and 16 located therebetween. Additionally, the alignment
elements 81 and the alignment recesses 82 co-operate with each other to
form a seal between first and second membranes 15 and 16 and the active
substance layer 3 and the needle support layer 5 and the drive substance
layer 19.

[0196] An additional advantage of providing the alignment elements 81 and
the alignment recesses 82 between the active substance layer 3 and the
needle support layer 5 is that they stretch the first membrane 15 taut
across the active substance chambers 4 and the corresponding membrane
accommodating recesses 25 which further enhances the reliability with
which the pressure of the active substance at which the first membrane
engages the puncturing members 33 and bursts can be set.

[0197] Referring now to FIGS. 15 and 16, there is illustrated a
micro-needle device according to another embodiment of the invention,
indicated generally by the reference numeral 85. The micro-needle device
85 is substantially similar to the micro-needle device 1, and similar
components are identified by the same reference numerals. The main
difference between the micro-needle device 85 and the micro-needle device
1 is that instead of the communicating means for accommodating the active
substance through the micro-needles 6 being provided by communicating
bores extending through the respective micro-needles 6, in this
embodiment of the invention each communicating means comprises the first
portion 29 of the communicating bore 28 extending through the needle
support layer 5, however the second portion of the communication bore 28
is replaced by a communicating channel 87 which communicates with the
first portion 29 of the communicating bore 28 and extends along an outer
surface 88 of the corresponding micro-needle 6. The communicating channel
87 of each micro-needle 6 is formed by a longitudinally extending recess
89 which extends in a generally axial direction along the corresponding
micro-needle 6 from a proximal end 90 towards the distal tip 27 of the
micro-needle 6, but terminates at a location 91 spaced apart from the
distal tip 27 in order that the distal tip 27 is formed by a pointed tip.
The first portion 29 of the communicating bore 28 extends through the
needle support layer 5 from an area 92 in the first major surface 23
which is substantially defined by the communicating channel 87.

[0198] A sealing ring 93 extends from the first major surface 23 of the
needle support layer 5 around each micro-needle 6, with the communicating
channel 87 located within the sealing ring 93 for sealably abutting the
skin of the subject in order to minimise leakage of the active substance
as the active substance is passing from the first portion 29 of the
communicating bore 28 into the communicating channel 87. Otherwise, the
micro-needle device 85 is similar to the micro-needle device 1 and its
use and operation is likewise similar.

[0199] Referring now to FIGS. 17 to 20, there is illustrated a
micro-needle device according to another embodiment of the invention,
indicated generally by the reference numeral 95. The micro-needle device
95 is substantially similar to the micro-needle device 1 and similar
components are identified by the same reference numerals. The main
difference between the micro-needle device 95 and the micro-needle device
1 is that a gasket 96 is located between the active substance layer 3 and
the first membrane 15 to enhance sealing between the first membrane 15
and the active substance layer 3 and the needle support layer 5. A gasket
accommodating recess 97 is formed into the first major surface 20 of the
active substance layer 3, and the gasket 96 is recessed into the gasket
accommodating recess 97. Openings 106 in the gasket 96 accommodate
portions 107 of the active substance layer 3 therethrough and communicate
the membrane accommodating recesses 25 with the active substance chambers
4. A plurality of annular projecting elements 98 extend from the second
major surface 24 of the needle support layer 3 around the respective
membrane accommodating recesses 25. The annular projecting elements 98
terminate in a radiused membrane abutting end 99 for sealably engaging
the first membrane 15 and for urging the first membrane 15 into sealable
engagement with the gasket 96, and for in turn urging the gasket 96 into
sealable engagement with the active substance layer 3. The gasket 96 is
of a deformable resilient material, in this embodiment of the invention
silicone material of approximately 40 shore hardness. Thus, the gasket 96
accommodates any variations in the depth of the annular projecting
elements 98 from the second major surface 24 of the needle support layer
5.

[0200] Accordingly, when the active substance layer 3 and the needle
support layer 5 are assembled and tightly secured together with the
gasket 96 in the gasket accommodating recess 97 and the first membrane 15
located between the needle support layer 5 and the gasket 96, the action
of the annular projecting elements 98 urging the first membrane 15 into
engagement with the gasket 96 and in turn urging the gasket 96 into
engagement with the active substance layer 3 effects a good seal between
the first membrane 15 and the gasket 96 and also between the gasket 96
and the active substance layer 3. Additionally, the action of the annular
projecting elements 98 on the first membrane 15 also effects a good seal
between the first membrane 15 and the needle support layer 5.

[0201] Additionally, when the active substance layer 3 and the needle
support layer 5 are tightly secured together, the action of the annular
projecting elements 98 on the first membrane 15 urging the first membrane
15 into the gasket 96 acts to stretch the first membrane 15 across the
membrane accommodating recesses 25 so that the first membrane 15 is
stretched taut across the membrane accommodating recesses 25. This, as
described with reference to the micro-needle device 80 described with
reference to FIG. 14, enhances the reliability and accuracy with which
the pressure of the active substance at which the first membrane 15
engages the puncturing members 33 and bursts can be set.

[0202] Additionally, in this embodiment of the invention peripheral edges
100 of the gasket accommodating recess 97 in the active substance layer 3
are radiused adjacent the barrier panels 40 of the adjacent active
substance chambers 4 to avoid any danger of rupturing of the first
membrane 15 during assembly of the active substance layer 3 and the
needle support layer 5. Peripheral edges 101 of the membrane
accommodating recesses 25 in the needle support layer 5 are also
radiused, to similarly avoid any danger of rupturing of the first
membrane 15 during assembly of the active substance layer 3 and the
needle support layer 5. Peripheral edges 102 of the active substance
chambers 4 adjacent the second major surface 21 of the active substance
layer 3 are radiused in order to avoid any danger of the second membrane
16 being ruptured as the second membrane 16 is being urged by the drive
substance into the active substance chambers 3.

[0203] In this embodiment of the invention the piercing points 35 of the
puncturing members 33 are centrally located in the corresponding membrane
accommodating recesses 25. However, the micro-needles 6 are offset
relative to the centre of the corresponding membrane accommodating
recesses 25.

[0204] Additionally, in this embodiment of the invention securing lugs 105
extend from the first major surface 20 of the active layer 3 adjacent the
periphery of the active substance layer 3 and also adjacent the centre of
the active substance layer 3. The securing lugs 105 are of polymer
material formed integrally with the active substance layer 3, and are
fuseable with the second major surface 24 of the needle support layer 5
in response to ultrasonic welding. Thus, during ultrasonic welding of the
active substance layer 3 to the needle support layer 5 when the active
substance layer 3 and the needle support layer 5 are clamped together,
the securing lugs partly melt and fuse to the active substance layer 3,
in order to secure and retain the active substance layer 3 and the needle
support layer 5 together, on removal of a clamp, with the first membrane
15 and the gasket 96 tightly clamped between the active substance layer 3
and the needle support layer 5. Although not shown, similar securing lugs
may be provided extending from one or both of the second major surface 21
of the active substance layer 3 and the first major surface 37 of the
drive substance layer 9 adjacent the peripheral edges and the centre
thereof for similarly fusing and securing the active substance layer 3
and the drive substance layer 9 together with the second membrane 16
clamped therebetween in tight sealable engagement with the active
substance and drive substance layers 3 and 9. Although not shown, similar
securing lugs may be provided on the second major surface 38 of the drive
substance layer 9 and/or on the first major surface 45 of the activation
layer 12 for tightly and sealably securing the drive substance layer 9
and the activation layer 12 with the third membrane 17 tightly and
sealably clamped therebetween.

[0205] Otherwise the micro-needle device 95 is similar to the micro-needle
device 1 and its use and operation is likewise similar.

[0206] While the annular projecting elements of the micro-needle device 75
have been described as being in sealable engagement with the adjacent
membrane whereby the sealing engagement is achieved by compression, it is
envisaged in certain cases that the annular projecting elements may be
bonded to the adjacent membrane. However, when bonding is provided
between the annular projecting elements and the adjacent membrane, it is
also envisaged that compression would also be relied on in order to
maintain the respective needle support layer, the active substance layer,
the drive substance layer and the activating layer assembled together
with the respective first, second and third membranes secured together.
Such a clamping arrangement may be provided by a clamping frame within
which the assembled layer 3, 5, 9 and 12 together with the membranes 15,
16 and 17 would be located.

[0207] While the micro-needle devices according to the invention have been
described as comprising active substance layers, drive substance layers
and needle support layers of polymer materials, the active substance
layer, the drive substance layer and the needle support layer may be of
any other suitable material. Needless to say, the activation layer may be
of a material other than ceramics or a material suitable for forming a
printed circuit board. It is envisaged that the activation layer may be
of a polymer material.

[0208] While the micro-needles of the micro-needle device 85 have been
described as comprising communicating channels extending in a generally
axial direction along the outer surface of the micro-needles, it is
envisaged that the communicating channels may extend in the form of a
spiral around the outer surface of the micro-needles.

[0209] While the micro-needle devices according to the invention have been
described as comprising a particular type of puncturing means, any other
suitable puncturing means may be provided. For example, it is envisaged
that the puncturing means may terminate in a piercing tip, which instead
of being pointed, may be of annular shape with a cutting edge, which
would form an opening in the first membrane. It is also envisaged that
the puncturing means may terminate in an elongated knife edge or a
serrated saw-type edge for engaging and piercing the first membrane.
Further, it is envisaged that where the puncturing means terminates in a
knife edge or a serrated saw-type edge, the knife edge or serrated
saw-type edge could be inclined relative to the plane defined by the
second major surface of the needle support layer to facilitate
progressive engagement of the first membrane with the knife edge or
serrated saw-type edge to further enhance rupturing of the first
membrane.

[0210] It is also envisaged that each puncturing member may terminate in a
partly annular cutting edge, which would extend partly around and
adjacent the periphery of the corresponding membrane accommodating
recess, in order to partly sever a portion of the first membrane from the
first membrane adjacent the corresponding membrane accommodating recess,
for communicating the communicating bore or channel of the micro-needle
with the corresponding active substance chamber.

[0211] It is also envisaged that the first membrane may be provided with
small areas of weakness at respective locations corresponding to the
locations which would be engaged by the puncturing means when the active
substance in the corresponding active substance chamber is pressurised
for urging the first membrane into engagement with the puncturing means.

[0212] From the above description of the micro-needle devices it will be
readily apparent to those skilled in the art that by varying the length
of the puncturing member, which in turn varies the distance of the
piercing point of the puncturing member from the plane defined by the
second major surface of the needle support layer, the pressure of the
active substance at which the first membrane bursts can be varied, which
in turn allows the pressure at which the active substance is delivered
through the communicating bore or the communicating channel of the
corresponding micro-needle to be controlled. As discussed above, by
varying the pressure at which the active substance is delivered through
the micro-needles, the injection velocity of the active substance into
the subject can also be varied, thereby allowing the depth to which the
active substance is delivered beneath the skin of the subject to be set.

[0213] It is also envisaged that the puncturing means may be provided to
be adjustable for selectively varying the distance d of the piercing
point or tip of the puncturing member from the plane defined by the
second major surface of the needle support layer. Such adjustability
could be achieved by providing each puncturing member as an elongated
spindle which would be axially moveable in a corresponding bore through
the needle support layer into the corresponding membrane accommodating
recess. The spindle of the puncturing member may be threaded and would
engage corresponding threads in the corresponding bore of the needle
support layer for facilitating selective adjustment of the distance d of
the piercing point or tip of the puncturing member from the plane defined
by the second major surface of the needle support layer.

[0214] While the puncturing means has been described as being located in
the needle support layer, it is envisaged that the puncturing means may
be provided in the active substance layer, and this would be a particular
requirement where the micro-needle device is to be used, or where some of
the active substance chambers of the micro-needle device are to be used
for withdrawing a substance, for example, blood or other bodily fluid
from a subject. In which case, it is envisaged that the micro-needle
device would be provided with the second membrane stretched into the
active substance chambers and defining the active substance chambers,
which could be under vacuum, or alternatively, the second membrane could
be pressurised by the driving substance in the corresponding drive
substance chambers. In this configuration of the micro-needle device, the
barrier panel would be omitted from the active substance chambers, and
the puncturing member would be located within the active substance
chamber with a puncturing point adjacent but spaced apart from the first
membrane. The drive substance would be of a material which on being
activated would contract. Thereby on being activated by a suitable
activating means, contraction of the drive substance would urge the
second membrane out of the active substance chamber, thereby reducing the
pressure in the active substance chamber. The reduction in pressure in
the active substance chamber would urge the first membrane to balloon
into the active substance chamber, which in turn would be engaged by the
piercing point of the puncturing member, which would then communicate the
low pressure or evacuated active substance chamber through the
communicating bore or channel of the corresponding micro-needle with a
location beneath the skin of the subject for withdrawing the bodily fluid
from the subject.

[0215] It is also envisaged that the micro-needle device may be provided
with a means for analysing the bodily fluid so withdrawn from the
subject. The microprocessor of the micro-needle device may be programmed
that in response to the analysis of the bodily fluid so withdrawn, one or
more of the activating means which correspond to active substance
chambers which contain a suitable active substance would be activated to
deliver the active substance from the corresponding active substance
chamber to the subject.

[0216] While the activating means have been described as comprising
heating elements, any other suitable activating means besides heating
elements may be provided. In certain cases, it is envisaged that the
activating means may be an element for cooling or chilling the drive
substance. In which case, the drive substance could, for example, be
provided by a fluid which rapidly contracted on being activated, for
example, on being subjected to a reduction in temperature. In which case,
the activating means would be provided to reduce the temperature of the
drive substance, instead of raising the temperature of the drive
substance.

[0217] It will also be appreciated that while the drive substance has been
described as comprising gas filled microspheres sold under the Trade Mark
EXPANCEL, gas filled polymer microspheres sold under other Trade Marks
may be used, and needless to say, other suitable drive substances may be
used, for example, the drive substance may be a gas, or may be provided
by a liquid which rapidly transitions from the liquid phase to the
gaseous phase on being heated, alternatively, the drive substance may be
provided by a porous polymer impregnated with a gas, which on being
heated either causes the polymer material to rapidly expand, or causes
the gas to migrate from the porous polymer material as it expanded for in
turn urging the second membrane into the corresponding active substance
chambers. It is also envisaged that the drive substance may be provided
in the form of a solid propellant, such as, for example, AIBN.

[0218] It will be appreciated that while the micro-needle devices have
been described for delivering a liquid medicament into a subject, the
micro-needle devices may be used for delivering any suitable medicament
or substance, whether in liquid or gaseous form into a subject.

[0219] It will also be appreciated that while the micro-needle device has
been described for transferring fluid between the active substance
chambers and a subject, which may be a human or animal subject, it is
envisaged that the micro-needle device may be used for transferring a
fluid between the first chamber and any other non-human or non-animal
object or device.

[0220] While the fluid transfer devices according to the invention have
been described as being micro-needle devices, the fluid transfer devices
may be of any other suitable configuration. For example, any other
suitable penetrating means for penetrating the skin of a subject besides
micro-needles extending from the skin abutting layer may be provided, and
such penetrating means may, for example, be provided by roughening the
first major surface of the skin abutting layer. In which case, it is
envisaged that the communicating means would be provided by communicating
bores extending through the skin abutting layer from the corresponding
membrane accommodating recesses to the first major surface of the skin
abutting layer.

[0221] It will also be appreciated that while the micro-needles have been
described as being of conical shape, the micro-needles may be of any
other suitable or desired shape, and in certain cases, may be of
transverse cross-section other than circular, for example, square,
rectangular, hexagonal, octagonal, polygonal or any other suitable or
desired shape, cross-section or configuration, and where the
micro-needles are of square cross-section, the micro-needles would be of
pyramid form. It is also envisaged that the micro-needles may be of
partly conical and partly pyramid shape.

[0222] It is also envisaged that the first membrane may be provided with a
plurality of areas of weakness, the locations of which would typically
correspond with the locations of the distal end of the corresponding
puncturing member, so that on engagement of the area of weakness of the
first membrane with the distal piercing end of the corresponding
puncturing member, the weakened area would be punctured, or
alternatively, the distal piercing end of the puncturing member would
cause rupturing of the first membrane adjacent the corresponding first
chamber. Indeed, in certain cases, it is envisaged that arcuate lines of
weakness, for example, partly annular lines of weakness could be provided
in the first membrane which would extend in a partly annular shape around
and typically adjacent the periphery of the corresponding first membrane
accommodating recesses. In which case, the cutting edge of the puncturing
member may be correspondingly shaped of partially annular shape and would
be configured to engage the corresponding line of weakness for rupturing
the first membrane along the line of weakness. Indeed, where the first
membrane is provided with such areas or lines of weakness, while it would
most likely be preferable, it would not be essential that the cutting
edge should correspond exactly with the line of weakness. In certain
cases, a pointed distal tip may be sufficient to cause rupturing of the
first membrane along the entire line of weakness. Such an arrangement of
lines of weakness in the first membrane and correspondingly shaped
cutting edges of the puncturing members would be particularly
advantageous in cases where the first membrane is provided as a foil
material, such as a metal foil.

[0223] While the first and second layers have been described and
illustrated as being of similar thickness, the thickness of the active
and drive substance layers may be the same or different. Indeed, in
certain cases, it is envisaged that the drive substance layer may be
thinner than the active substance layer or vice versa, and this would
largely depend on the type of drive substance being used. Where gas
filled spheres of the type sold under EXPANCEL is provided as the drive
substance, and since such gas filled spheres can expand up to four times
and more their normal size, it is envisaged that the thickness of the
drive substance layer may be less than the thickness of the active
substance layer.

[0224] Additionally, while the active and drive substance chambers have
been described as being of circular transverse cross-section, the first
and second chambers may be of any desired cross-section.

[0225] It is also envisaged that a spacer layer, which typically would be
of a polymer material, may be provided located between the needle support
layer 5 and the first membrane 15. The spacer layer would be provided
with openings corresponding to and aligned with the membrane
accommodating recesses 25, and the openings in the spacer layer would
typically be of diameter similar to the diameter of the membrane
accommodating recesses 25 for accommodating the first membrane into the
membrane accommodating recesses 25 in the needle support layer 5. The
advantage of providing such a spacer layer between the needle support
layer 5 and the first membrane 15 is that it would facilitate increasing
the distance d between the piercing points 35 of the puncturing members
53 and the first membrane 15. This would result in an increase in the
pressure of the active substance within the active substance chambers 4
at which the first membrane 15 engaged the piercing points 35 of the
puncturing members 33, and thus, would allow the predefined pressure of
the active substance in the active substance chambers 4 at which the
first membrane 15 bursts to be set at a higher pressure, for in turn
increasing the injection velocity at which the active substance is
injected into the subject. It is also envisaged that spacer layers of
different thicknesses may be provided, so that the injection velocity of
the active substance could be set by selecting a spacer element of the
appropriate thickness for locating between the needle support layer 5 and
the first membrane 15.

[0226] While the micro-needle devices have been described as comprising an
activation layer which is separate from the drive substance layer, in
certain cases, it is envisaged that the activation layer may be formed
integrally with the drive substance layer. In which case the heating
elements or other activating means together with the corresponding
circuitry would be appropriately located in or on the portion of the
drive substance layer which forms the activation layer. By integrally
forming the drive substance and activation layers, the need for the third
membrane would be avoided.

[0227] While in general the micro-needle devices according to the
invention have been described with the active substance layer, the drive
substance layer, the needle support layer and the activation layer
secured together by clamping or by ultrasonic welding, in certain cases,
it is envisaged that the respective layers may be bonded to the
corresponding membrane by a suitable bonding agent, for example, a
suitable adhesive. However, the advantage of securing the layers together
with the membranes located therebetween by clamping or by ultrasonic
welding is that the need for adhesive or other such bonding agents is
avoided, and this could be advantageous in certain cases where the active
substance would react with certain adhesives or bonding agents.

[0228] While the micro-needle devices have been described as comprising a
plurality of micro-needles, active substance chambers, drive substance
chambers and activating means, it is envisaged that a micro-needle device
may be provided with one single micro-needle, one single active substance
chamber, one single drive substance chamber and one single activating
means. It is also envisaged that in certain cases the numbers of
micro-needles, active substance chambers, drive substance chambers and
activating means may be different in the one micro-needle device. For
example, in certain cases, it is envisaged that more micro-needles may be
provided than active substance chambers. Alternatively, less
micro-needles than active substance chambers may be provided. Similarly,
more or less drive substance chambers than active substance chambers may
be provided, and additionally, more or less activating means than drive
substance chambers may be provided.